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Completed

NCT Number: NCT04829773

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.

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Key information

Conditions

Fibrodysplasia Ossificans Progressiva Muscular Diseases Musculoskeletal Diseases Myositis Myositis Ossificans

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cambridge Ipsen US

Cambridge, Massachusetts, 02142, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

Treatment and study plan

Palovarotene

Drug

oral capsules

midazolam

Drug

oral syrup

Primary outcomes

  1. Maximum (peak) observed plasma drug concentration

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

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

    Time frame: 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

    Time frame: 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)

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

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

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

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

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

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

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

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

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

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

    Time frame: 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

    Time frame: Days 1, 2, 15, 16

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

    Time frame: Days 1, 2, 15, 16

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

    Time frame: Days 1, 2, 15, 16

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

    Time frame: 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

    Time frame: Days 1, 2, 15, 16

  14. Accumulation ratio for DDI cohort

    Time frame: Days 1, 2, 15, 16

Secondary outcomes

  1. Occurrence of Adverse Events (AEs)

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

Sponsors and collaborators

Lead sponsor

Clementia Pharmaceuticals Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
Apr 2, 2021
Registry last updated
Apr 2, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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