This page shows what was measured, who it was measured in, and what that does not settle.
What Cinacalcet does in the body
Overactive parathyroid glands, mainly in people on dialysis, and high blood calcium caused by a parathyroid tumour
The parathyroid gland has a sensor on its surface that reads how much calcium is in the blood. This drug does not block that sensor or imitate calcium. It binds to a different part of the same sensor and makes it more responsive, so the same amount of calcium produces a louder signal. The gland concludes calcium is adequate and releases less hormone — and because it is not raising calcium to achieve this, calcium falls rather than rises.
What happened in people
Primary composite cardiovascular endpoint 48.2% against 49.2%, relative hazard 0.93 (95% CI 0.85 to 1.02), P=0.11
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
The limit that matters most
EVOLVE remains one of the most argued-over trials in nephrology, and it has not been repeated
Where it acts
The surface of the parathyroid chief cell — the sensor that decides how much parathyroid hormone the gland releases
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 1K860WSG25 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 120 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Time to death, myocardial infarction, hospitalisation for unstable angina, heart failure or a peripheral vascular event
✗ The study did not show it
Who was studied
EVOLVE (NCT00345839)
How many people
3883
Study design
Phase 3, randomised, double-blind, placebo-controlled, up to 64 months
Compared against
A dummy treatment
Kind of result
Living longer, or avoiding a major event
What was found
48.2% against 49.2%; relative hazard 0.93 (95% CI 0.85 to 1.02), P=0.11 in the prespecified unadjusted intention-to-treat analysis
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Median study-drug exposure was 21.2 months on cinacalcet against 17.5 on placebo, and placebo patients could receive commercial cinacalcet after discontinuing. Hypocalcaemia and gastrointestinal adverse events were significantly more frequent on treatment.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken with food
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
Cinacalcet United States prescribing information (openFDA label endpoint) — indications and limitations of use, warnings and precautions, clinical pharmacolo… · a recorded source, not a stored snapshot
First clinical fracture event
✗ The study did not show it
Who was studied
EVOLVE prespecified fracture analysis (Moe 2015)
How many people
3883
Study design
Prespecified secondary endpoint of the same randomised trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Unadjusted relative hazard 0.89 (95% CI 0.75 to 1.07); adjusted 0.83 (0.72 to 0.98); lag-censored 0.72 (0.58 to 0.90); censored at cointervention 0.71 (0.58 to 0.87)
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The paper reports the unadjusted null and the adjusted positive with equal prominence. Secondary citations of it overwhelmingly quote the adjusted figures.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken with food
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
Cinacalcet United States prescribing information (openFDA label endpoint) — indications and limitations of use, warnings and precautions, clinical pharmacolo… · a recorded source, not a stored snapshot
What we know
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Cinacalcet
What a person takes: Oral tablet, taken with food.
The measurement behind this step
Swallowed whole with a meal, because a high-fat meal raises exposure by roughly two-thirds against fasting. Nausea and vomiting are among the commonest reasons it is stopped, which is what motivated the development of an intravenous calcimimetic given by the dialysis unit.
Getting in
Swallowed daily, and much better absorbed with food
A tablet taken once or twice a day. Taking it with a meal substantially increases how much gets into the blood.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Maximum plasma concentration is reached in about 2 to 6 hours. A high-fat meal raises Cmax by 82% and AUC by 68% against fasting; a low-fat meal raises them 65% and 50%. Concentrations then decline biphasically with an initial half-life of about 6 hours and a terminal half-life of 30 to 40 hours.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
Getting in
It reaches the parathyroid gland’s calcium sensor
The molecule spreads widely through the body and finds a receptor that sits on the surface of the cells in the parathyroid gland.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Volume of distribution is approximately 1000 L, indicating extensive tissue distribution, with 93% to 97% plasma protein binding. The target is the calcium-sensing receptor, a class C G-protein-coupled receptor whose principal role is regulating parathyroid hormone synthesis and secretion.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
What it acts on
It binds a different part of the receptor from calcium
Calcium binds at the outside end of the receptor. This drug binds within the part embedded in the membrane, somewhere else entirely.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The binding site is in the seven-transmembrane domain, spatially separate from the large extracellular Venus flytrap domain where calcium binds. That separation is what makes the drug an allosteric modulator rather than a competitor, and it is why the receptor still requires calcium to respond.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
The change it makes
The sensor now reads the same calcium as higher
Nothing about the blood has changed, but the gland behaves as though calcium had risen. It releases less hormone.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Positive allosteric modulation shifts the calcium concentration-response curve leftward without raising the maximal response. Receptor activation raises intracellular calcium through Gq and phospholipase C and suppresses parathyroid hormone secretion and, over time, synthesis. Intact parathyroid hormone reaches its nadir 2 to 6 hours after a dose, tracking the plasma concentration.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
What that does for a person
Calcium falls with the hormone rather than rising
Less parathyroid hormone means less calcium pulled out of bone and less reabsorbed by the kidney, so calcium in blood goes down. That is the opposite of what a vitamin D drug does.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label states the reduction in parathyroid hormone is associated with a concomitant decrease in serum calcium. Because the calcium fall is intrinsic to the mechanism rather than an off-target effect, hypocalcaemia is the dose-limiting toxicity and cannot be engineered away within this class.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
What that does for a person
The biochemistry moves reliably; the outcomes are contested
Parathyroid hormone comes down, which is what the drug is prescribed for. Whether that means fewer deaths, heart attacks or fractures depends entirely on which analysis of the same trial you read.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
EVOLVE primary composite relative hazard 0.93 (95% CI 0.85 to 1.02, P=0.11) unadjusted. Fracture relative hazard 0.89 (0.75 to 1.07) unadjusted, 0.83 (0.72 to 0.98) adjusted for baseline and multiple fractures, 0.72 (0.58 to 0.90) with lag censoring and 0.71 (0.58 to 0.87) censoring at cointervention. Every correction moves the estimate the same way and none of them is a randomised comparison.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults on dialysis with secondary hyperparathyroidism, and adults with hypercalcaemia from parathyroid carcinoma or from primary hyperparathyroidism when surgery is not possible.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and efficacy of cinacalcet have not been established in pediatric patients.”
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-30
On older people, the label states: “Of the total number of subjects (n=1136) in clinical studies of cinacalcet, 26 percent were 65 and over, and 9 percent were 75 and over.”
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Limited case reports of cinacalcet use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes.”
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data regarding the presence of cinacalcet in human milk or effects on the breastfed infant or on milk production.”
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-30
On people with reduced liver function, the label states: “Patients with moderate and severe hepatic impairment should have serum calcium, serum phosphorus, and iPTH levels monitored closely throughout treatment with cinacalcet because cinacalcet exposure (AUC 0-infinite ) is increased by 2.4 and 4.2 fold, respectively, in these patients [see Clinical Pharmacology (12.3)].”
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-30
On people with reduced kidney function, the label states: “No dosage adjustment is necessary for renal impairment [see Clinical Pharmacology ( 12.3) ] .”
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-30
Where the result stopped carrying
The primary endpoint of a 3883-patient, 64-month trial was missed at P=0.11
Differential exposure of 21.2 against 17.5 months, plus access to commercial drug after discontinuation, left the intention-to-treat comparison diluted
Hypocalcaemia has caused life-threatening events and deaths, including in children, and the drug has no established paediatric safety
Suppressing parathyroid hormone below 100 pg/mL can produce adynamic bone disease, an iatrogenic version of the problem being treated
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet, taken with food
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Swallowed whole with a meal, because a high-fat meal raises exposure by roughly two-thirds against fasting. Nausea and vomiting are among the commonest reasons it is stopped, which is what motivated the development of an intravenous calcimimetic given by the dialysis unit.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
No boxed warning. Hypocalcaemia is the defining risk and can cause paraesthesias, myalgias, muscle spasms, tetany, seizures, QT prolongation and ventricular arrhythmia; life-threatening events and fatal outcomes have been reported, including in children, and safety in children has not been established. Not indicated in chronic kidney disease without dialysis. Further labelled warnings cover upper gastrointestinal bleeding in patients with risk factors, postmarketing reports of hypotension, worsening heart failure and arrhythmia in impaired cardiac function, and adynamic bone disease if intact parathyroid hormone falls below 100 pg/mL. Cinacalcet is a strong CYP2D6 inhibitor.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
EVOLVE — Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (NCT00345839) · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet, taken with food
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Nausea and vomiting are among the commonest reasons it is stopped, which is what motivated the development of an intravenous calcimimetic given by the dialysis unit.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
68 products list this as an active ingredient in the United States drug directory. 68 of them contain it and nothing else.
FDA National Drug Code directory · 72162-2527 · read 2026-08-29
They are sold as powder, tablet, tablet, coated and tablet, film coated, taken oral.
FDA National Drug Code directory · 72162-2527 · read 2026-08-29
The regulator's established pharmacologic class for it is calcium-sensing receptor agonist [epc] and increased calcium-sensing receptor sensitivity [moa].
FDA National Drug Code directory · 72162-2527 · read 2026-08-29
28 published labels name it as an active ingredient. 28 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-29
Cinacalcet is oral at 3 DOSAGE FORMS & STRENGTHS Cinacalcet tablets is available as film-coated tablets., recorded as fda label in effect 2026-02-27 in the United States.
US prescribing information · 55f95ae0-84ac-4ae4-b7a0-7590ab919ae1 · read 2026-08-30
Recorded price in US: 0.40219–1.03674 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 30 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Cinacalcet studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the trial showed a cardiovascular benefit — its declared analysis did not, and it is routinely cited as though the adjusted analysis were the result
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the fracture reduction of 16% to 29% is established, when it appears only after adjustments that dissolve the randomisation
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That lowering parathyroid hormone is itself the benefit, rather than a surrogate for outcomes the trial could not demonstrate
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the drug is suitable in chronic kidney disease before dialysis — the label states the opposite, on hypocalcaemia grounds
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Cinacalcet are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
EVOLVE missed its primary endpoint in the analysis it declared
In plain words
The largest trial of this drug enrolled 3883 dialysis patients and followed them for up to five years. In the analysis it had committed to in advance, deaths and major cardiovascular events were not significantly reduced.
What was measured
Primary composite endpoint relative hazard 0.93 (95% CI 0.85 to 1.02), P=0.11 — not met
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
EVOLVE randomised 3883 haemodialysis patients with moderate-to-severe secondary hyperparathyroidism — median intact parathyroid hormone 693 pg/mL — to cinacalcet or placebo, with all patients eligible for conventional therapy including phosphate binders and vitamin D sterols, and followed them for up to 64 months. The primary composite of death, myocardial infarction, hospitalisation for unstable angina, heart failure or a peripheral vascular event occurred in 938 of 1948 (48.2%) on cinacalcet and 952 of 1935 (49.2%) on placebo, relative hazard 0.93 (95% CI 0.85 to 1.02, P=0.11), in the prespecified intention-to-treat analysis. Median study-drug exposure was 21.2 months on cinacalcet against 17.5 months on placebo, a difference that is itself part of the interpretive problem. Hypocalcaemia and gastrointestinal adverse events were significantly more frequent on cinacalcet.
Written into the record, not signed off as a reviewed claim
The fracture endpoint tells the same story: null unadjusted, positive adjusted
In plain words
Clinical fractures were counted as a planned secondary outcome. Unadjusted, there was no significant difference. Adjusted for baseline differences and repeated fractures it became significant, and adjusted further for how long people actually took the drug it grew larger.
What was measured
That cinacalcet reduces fractures — the declared unadjusted analysis says it does not, and every adjusted analysis says it does by between 16% and 29%
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Clinical fractures occurred in 255 of 1935 placebo patients (13.2%) and 238 of 1948 cinacalcet patients (12.2%). Unadjusted intention-to-treat relative hazard was 0.89 (95% CI 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures it was 0.83 (0.72 to 0.98). Using the prespecified lag-censoring analysis, a measure of actual drug exposure, it was 0.72 (0.58 to 0.90); censoring at cointerventions such as parathyroidectomy, transplantation or commercial cinacalcet gave 0.71 (0.58 to 0.87). The authors state both halves plainly: in the unadjusted intention-to-treat analysis cinacalcet did not reduce fracture, and after accounting for baseline differences, multiple fractures and discontinuation it reduced fracture by 16% to 29%. Every adjustment moves the estimate the same way, which is either a real effect obscured by crossover and dropout, or the signature of analytical flexibility. The trial cannot distinguish between those.
Written into the record, not signed off as a reviewed claim
Low calcium is the defining harm, and it has been fatal
In plain words
Because the drug works by lowering calcium, pushing it too far is the main danger. The label records life-threatening events and deaths associated with low calcium, including in children, and the drug is not approved for children.
What was measured
Hypocalcaemia and gastrointestinal adverse events significantly more frequent than placebo in 3883 randomised patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that significant lowering of serum calcium can cause paraesthesias, myalgias, muscle spasms, tetany, seizures, QT prolongation and ventricular arrhythmia, and that life-threatening events and fatal outcomes associated with hypocalcaemia have been reported, including in paediatric patients. Safety and effectiveness in children have not been established. The drug is explicitly not indicated in chronic kidney disease without dialysis because of increased hypocalcaemia risk. Other labelled warnings cover upper gastrointestinal bleeding in patients with risk factors, postmarketing reports of hypotension, worsening heart failure and arrhythmia in impaired cardiac function, and adynamic bone disease if intact parathyroid hormone is suppressed below 100 pg/mL — the last being an iatrogenic bone disease produced by treating the bone disease.
Source
Cinacalcet United States prescribing information, Warnings and Precautions 5.1 to 5.4 and Indications and Usage Limitations (openFDA label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
It is a modulator, not an agonist, and that distinction is the safety margin
In plain words
The drug does not switch the calcium sensor on. It makes the sensor more responsive to the calcium already there. That means its effect is bounded by how much calcium is present rather than being open-ended.
What was measured
Intact parathyroid hormone nadir 2 to 6 hours post dose, matching Cmax; steady state within 7 days
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Cinacalcet binds the transmembrane domain of the calcium-sensing receptor, away from the extracellular calcium-binding site, and increases the receptor’s sensitivity to activation by extracellular calcium. The label describes it as a calcimimetic that directly lowers parathyroid hormone by increasing that sensitivity, with the reduction in parathyroid hormone accompanied by a concomitant fall in serum calcium. The pharmacodynamic signature is a leftward shift in the calcium-response curve rather than a raised baseline response: the nadir in intact parathyroid hormone occurs 2 to 6 hours after a dose, matching the maximum plasma concentration, and serum calcium then remains constant across the dosing interval once steady state is reached within 7 days.
Source
Cinacalcet United States prescribing information, Clinical Pharmacology 12.1 and 12.2 (openFDA label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A drug whose exposure was 21 months against a placebo group’s 17.5
In plain words
The two groups did not take their assigned treatment for the same length of time. That difference on its own can move a result in a long trial, and it is why the adjusted analyses exist at all.
What was measured
That the intention-to-treat null is the final answer, or that the adjusted positives are — neither analysis is clean, and the trial has not been repeated
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Median duration of study-drug exposure was 21.2 months on cinacalcet against 17.5 months on placebo, in a trial with up to 64 months of follow-up. Differential discontinuation in a trial of this length undermines an intention-to-treat comparison in the direction of the null, because placebo patients who left the study could and did receive commercial cinacalcet — which is precisely what the censoring-at-cointervention analysis of the fracture endpoint was designed to handle, and which returned a relative hazard of 0.71. Interpreting this trial therefore requires choosing between an analysis that is unbiased by design but diluted by crossover, and analyses that correct for crossover at the cost of no longer being randomised comparisons.
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What is not here
7 questions this page could not answer
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What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
The first calcimimetic — a molecule that binds the calcium-sensing receptor away from the calcium site and makes it read the same calcium as higher — whose 3883-patient cardiovascular outcome trial missed its primary endpoint in the unadjusted intention-to-treat analysis at a hazard ratio of 0.93 (95% CI 0.85 to 1.02, P=0.11), and whose prespecified fracture endpoint was likewise null unadjusted at 0.89 (0.75 to 1.07) and positive after adjustment at 0.83 (0.72 to 0.98).
Recorded evidence blocks (10)
Q1
On the Cinacalcet label: indicated for what?
"1 INDICATIONS & USAGE Cinacalcet is a positive modulator of the calcium sensing receptor indicated for: Secondary Hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis. (1.1) Limitations of Use: Cinacalcet is not indicated for use in patients with CKD who are not on dialysis.": indications and usage on Cinacalcet's label. DailyMed label · 330b4214-dba7-468c-a67e-b1057f4628da · 2026-06-16
Q2
71 registered trials of Cinacalcet — at which phases?
"Based on information in IRB archives the study was terminated in 2009 due to low enrollment"; 7 of 71 registered studies
Show the evidence
Trial
NCT00415584
terminated; "Based on information in IRB archives the study was terminated in 2009 due to low enrollment"
NCT00446329
terminated; "due to financial problems"
NCT01011114
terminated; "Study was not renewed with the IRB"
NCT01011699
terminated; "Financial problem"
NCT01277510
terminated; "Study was put on clinical hold on 30 Jan 2013 following a subject fatality. Study was never restarted and was closed."
NCT01439867
terminated; "Amgen decided to terminate the study early to be able to meet US regulatory timelines fo filing. Subjects in treatment were rolled over to the 20140159 study."
1 further recorded trialNCT02138838
terminated; "Amgen decided to terminate the study early to be able to meet US regulatory timelines fo filing. Subjects in treatment were rolled over to the 20140159 study."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Cinacalcet used Cinacalcet 60 MG — over how long?
Human studies of Cinacalcet used "Cinacalcet 60 MG". ClinicalTrials.gov · 2026-09-01
2 recorded entries; human; also "Cinacalcet 30 mg Tablet"
Show the evidence
human
NCT01519037
Cinacalcet 60 MG
NCT03027557
Cinacalcet 30 mg Tablet
recorded 2026-09-01 · last checked 2026-09-04
Q5
Cinacalcet's half-life is 6 hours — which schedules were studied?
6 hours, the half-life Cinacalcet's label states: "After absorption, cinacalcet concentrations decline in a biphasic fashion with an initial half-life of approximately 6 hours and terminal half-life of 30 to 40 hours." DailyMed label · 330b4214-dba7-468c-a67e-b1057f4628da · 2026-06-16
Show the evidence
half lifepharmacokinetics
6 hours; After absorption, cinacalcet concentrations decline in a biphasic fashion with an initial half-life of approximately 6 hours and terminal half-life of 30 to 40 hours.
metabolismpharmacokinetics
Metabolism and Excretion Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2.
recorded 2026-06-16 · last checked 2026-09-04
Q6
Which 33 trials of Cinacalcet posted no result?
Posted no result
33 of 33 completed trials
Registrations
NCT03774771, NCT03776058, NCT00936650, NCT00037635, NCT00527267 and NCT00042653, and 27 more
Completion dates
oldest 1999-12-13; newest 2024-01-22
Show the evidence
Trial
NCT03774771
1999-12-13
NCT03776058
2000-12-26
NCT00936650
2001-06
NCT00037635
2003-03
NCT00527267
2003-04
NCT00042653
2003-07
14 further recorded trials
NCT00527085
2003-08
NCT00132431
2005-07
NCT00936988
2005-12
NCT00117052
2006-02
NCT00135304
2006-12
NCT00336739
2007-03
NCT00195936
2008-02
NCT00952094
2009-06
NCT00656032
2010-01
NCT01101113
2012-06
NCT01599962
2012-08
NCT02417389
2012-12
NCT01103206
2013-02
NCT01143987
2013-02
Q7
At the median, Cinacalcet's trials enrolled 67 people — anything larger?
Median enrolment
67
Largest enrolment
3883
Registered trials counted
69
Q8
What do 10549 spontaneous reports say about Cinacalcet — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Cinacalcet appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 10549 reaction mentions were counted: hospitalisation 4873; laboratory test abnormal 3137; abdominal discomfort 530; blood parathyroid hormone increased 405. FAERS via Open Targets · CHEMBL1200776 · 2026-06-24
Show the evidence
hospitalisation
4873
laboratory test abnormal
3137
abdominal discomfort
530
blood parathyroid hormone increased
405
unevaluable event
386
hypocalcaemia
282
4 more recorded rows
blood calcium decreased
269
hypophagia
257
blood parathyroid hormone abnormal
205
hospice care
205
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Cinacalcet's label not list?
Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet.
drug_interactions
( 7.1 ) Cinacalcet is a strong inhibitor of CYP2D6.
drug_interactions
Dose adjustments may be required for concomitant medications that are predominantly metabolized by CYP2D6.
drug_interactions
( 7.2 ) 7.1 Strong CYP3A4 Inhibitors Cinacalcet is partially metabolized by CYP3A4.
drug_interactions
Dose adjustment of cinacalcet may be required if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole).
drug_interactions
7.2 CYP2D6 Substrates Cinacalcet is a strong inhibitor of CYP2D6.
2 more recorded rows
Interaction statementdrug_interactions
Dose adjustments may be required for concomitant medications that are predominantly metabolized by CYP2D6 (e.g., desipramine, metoprolol, and carvedilol) and particularly those with a narrow therapeutic index (e.g., flecainide and most tricyclic antidepressants) [see Clinical Pharmacology ( 12.3) ] .
Interaction statementpharmacokinetics
Metabolism and Excretion Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2.
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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