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AzTrials

Fibrodysplasia Ossificans ProgressivaPhase 1NCT04829773

Study Evaluating the Effect of Food on the Pharmacokinetics of Palovarotene and the Effect of Palovarotene on the Pharmacokinetics of the CYP3A4 Substrate Midazolam in Two Cohorts of Healthy Adult Subjects

A Phase 1 study testing Palovarotene and midazolam in people with Fibrodysplasia Ossificans Progressiva, run by Clementia Pharmaceuticals Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Study to evaluate the effect of food and the effect of swallowing capsule whole versus sprinkling on apple sauce on the pharmacokinetics (PK)/bioavailability of palovarotene, and evaluate the effect of palovarotene on the PK of the CYP3A4 substrate midazolam. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Fibrodysplasia Ossificans Progressiva
What is being tested?
Palovarotene and midazolam
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited States
Study dates
3 Jan 2019to 29 Mar 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Generally healthy male or female aged 18 to 55 years, inclusive; body mass index (BMI) of 18 to 30 kg/m2 and a body weight of >50 kg; resting pulse of >45 bpm and <100 bpm; systolic and diastolic blood pressure of <140/90 mmHg

Who cannot join

  • a history or current evidence of a clinically significant or uncontrolled disease, disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs
  • exposure to synthetic oral retinoids or creams containing retinoids in the past 30 days prior to the signature of the informed consent.
  • history or presence of silent infections, including positive tests for human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), hepatitis B virus (HBV), or hepatitis C virus (HCV)
  • history of allergy or hypersensitivity to retinoids, gelatin, or lactose
  • For the DDI component only, the subject had a history of allergy or hypersensitivity to benzodiazepines, midazolam, cherries, or midazolam formulation excipients

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cambridge Ipsen US

    Cambridge, Massachusetts, 02142

Other trials in United States

About this study

Official title: An Open-Label Study Evaluating the Effect of Food on the Pharmacokinetics of Palovarotene and the Effect of Palovarotene on the Pharmacokinetics of the CYP3A4 Substrate Midazolam in Two Cohorts of Healthy Adult Subjects

Study to evaluate the effect of food and the effect of swallowing capsule whole versus sprinkling on apple sauce on the pharmacokinetics (PK)/bioavailability of palovarotene, and evaluate the effect of palovarotene on the PK of the CYP3A4 substrate midazolam.

Being tested
Palovarotene, midazolam
Medical subject headings
Myositis Ossificans

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PalovaroteneDrug

    oral capsules

  • midazolamDrug

    oral syrup

Study groups in NCT04829773
Study groupRoleWhat they receive
PK Cohort 1ExperimentalSubjects received three single oral doses of palovarotene on Days 1, 6, and 11, separated by 5-day washout periods. Sequence A-B-C: Subjects received a single oral dose of palovarotene whole capsule under fasting conditions (at least a 10-hour overnight fast); followed by a single oral dose of palovarotene whole capsule 30 minutes after the start of a standardized high-fat, high-caloric breakfast; and then followed by a single oral dose of palovarotene sprinkled on 1 teaspoon of apple sauce, administered 30 minutes after the start of a standardized high-fat, high-caloric breakfast.
Receives: Drug: Palovarotene
PK Cohort 2ExperimentalSubjects received three single oral doses of palovarotene on Days 1, 6, and 11, separated by 5-day washout periods. Sequence B-C-A: Subjects received a single oral dose of palovarotene whole capsule 30 minutes after the start of a standardized high-fat, high-caloric breakfast; followed by a single oral dose of palovarotene sprinkled on 1 teaspoon of apple sauce, administered 30 minutes after the start of a standardized high-fat, high-caloric breakfast; and then followed by a single oral dose of palovarotene whole capsule under fasting conditions (at least a 10-hour overnight fast).
Receives: Drug: Palovarotene
PK Cohort 3ExperimentalSubjects received three single oral doses of palovarotene on Days 1, 6, and 11, separated by 5-day washout periods. Sequence C-A-B: Subjects received a single oral dose of palovarotene sprinkled on 1 teaspoon of apple sauce, administered 30 minutes after the start of a standardized high-fat, high-caloric breakfast; followed by a single oral dose of palovarotene whole capsule under fasting conditions (at least a 10-hour overnight fast); and then followed by a single oral dose of palovarotene whole capsule 30 minutes after the start of a standardized high-fat, high-caloric breakfast.
Receives: Drug: Palovarotene
Drug-Drug interaction (DDI) CohortExperimentalOn the morning of Day 1, subjects received a single dose of midazolam 30 minutes after the start of a standardized breakfast. On Day 2 (after the 24-hour midazolam blood draw) through Day 15, subjects received a daily, single dose of palovarotene in the morning 30 minutes after the start of a standardized breakfast. A second dose of midazolam was administered on Day 15 in the morning (immediately following the palovarotene dose) 30 minutes after the start of a standardized breakfast.
Receives: Drug: Palovarotene; Drug: midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum (peak) observed plasma drug concentration

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13.

  2. Time to reach maximum (peak) (t max) observed plasma concentration following drug administration

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13

  3. Area under the plasma concentration time (AUC 0-last) curve from time zero to the last quantifiable time point, calculated by linear-log trapezoidal summation

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13

  4. Area under the plasma concentration time curve from time zero to infinity (AUC 0-infinity)

    calculated by linear-log trapezoidal summation and extrapolated to infinity by addition of the last quantifiable plasma concentration divided by the elimination rate constant

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13

  5. Apparent terminal disposition rate constant/terminal rate constant yz

    determined by linear regression of the terminal points of the log-linear plasma concentration-time curve

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13

  6. Apparent terminal elimination half-life (t1/2)

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13

  7. Apparent volume of distribution after oral administration (Vd/F)

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13

  8. Apparent total clearance of the drug from plasma after oral administration (cLF)

    Measured: Days 1, 2, 3, 6, 7, 8, 11, 12, 13

  9. Area under the plasma concentration time curve from time zero to 24 hours only for DDI cohort

    Measured: Days 1, 2, 15, 16

  10. The last concentration before the next study drug administration at steady state for DDI cohort

    Measured: Days 1, 2, 15, 16

  11. Maximum (peak) observed plasma drug concentration at steady state for DDI cohort

    Measured: Days 1, 2, 15, 16

  12. Time to reach maximum (peak) observed plasma concentration following drug administration at steady state for DDI cohort

    Measured: Days 1, 2, 15, 16

  13. Minimum observed plasma concentration at steady state, taken as the lowest plasma concentration during dosing interval for DDI cohort

    Measured: Days 1, 2, 15, 16

  14. Accumulation ratio for DDI cohort

    Measured: Days 1, 2, 15, 16

Secondary outcomes (1)

  1. Occurrence of Adverse Events (AEs)

    Measured: from baseline until the end of study (16 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2021
  2. Study start3 Jan 2019
  3. Primary completion29 Mar 2019
  4. Study completion29 Mar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
This study had two components. One component evaluated the effect of food and the effect of swallowing capsule whole versus sprinkling on apple sauce on the PK/bioavailability of palovarotene, and the other component evaluated the effect of palovarotene on the PK of the CYP3A4 substrate midazolam. The PK of palovarotene after single and multiple doses was also evaluated as part of the DDI component. Two cohorts of healthy adult subjects were enrolled, one for each component.
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04829773
Sponsor's protocol ID
PVO-1A-102
Status last verified
Apr 2021
First submitted
1 Apr 2021
Last updated
2 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Marino R, Dube L, Ogier J, Le Quan Sang KH. The Pharmacokinetic Profile of Palovarotene: An Open-Label Phase I Trial Investigating the Effect of Food and Potential for Drug-Drug Interaction in Healthy Participants. Eur J Drug Metab Pharmacokinet. 2023 Nov;48(6):691-707. doi: 10.1007/s13318-023-00856-2. Epub 2023 Oct 7.

    PubMed 37804430

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Palovarotene and midazolam in people with Fibrodysplasia Ossificans Progressiva, run by Clementia Pharmaceuticals Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum (peak) observed plasma drug concentration (time frame: Days 1, 2, 3, 6, 7, 8, 11, 12, 13.). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04829773, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2021.

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