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

Fibrodysplasia Ossificans Progressiva Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04829773
• Other study ID #: PVO-1A-102
• Status: Completed
• Phase: Phase 1
• Start date: January 3, 2019
• Est. completion date: March 29, 2019

Study information

• Verified date: April 2021
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: March 29, 2019
• Est. primary completion date: March 29, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrodysplasia Ossificans Progressiva

Intervention

Drug:
• Palovarotene
oral capsules
• midazolam
oral syrup

Locations

Country	Name	City	State
United States	Cambridge Ipsen US	Cambridge	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Clementia Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum (peak) observed plasma drug concentration		Days 1, 2, 3, 6, 7, 8, 11, 12, 13.
Primary	Time to reach maximum (peak) (t max) observed plasma concentration following drug administration		Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Primary	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		Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Primary	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	Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Primary	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	Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Primary	Apparent terminal elimination half-life (t1/2)		Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Primary	Apparent volume of distribution after oral administration (Vd/F)		Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Primary	Apparent total clearance of the drug from plasma after oral administration (cLF)		Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Primary	Area under the plasma concentration time curve from time zero to 24 hours only for DDI cohort		Days 1, 2, 15, 16
Primary	The last concentration before the next study drug administration at steady state for DDI cohort		Days 1, 2, 15, 16
Primary	Maximum (peak) observed plasma drug concentration at steady state for DDI cohort		Days 1, 2, 15, 16
Primary	Time to reach maximum (peak) observed plasma concentration following drug administration at steady state for DDI cohort		Days 1, 2, 15, 16
Primary	Minimum observed plasma concentration at steady state, taken as the lowest plasma concentration during dosing interval for DDI cohort		Days 1, 2, 15, 16
Primary	Accumulation ratio for DDI cohort		Days 1, 2, 15, 16
Secondary	Occurrence of Adverse Events (AEs)		from baseline until the end of study (16 days)