Study To Evaluate The Effect Of Multiple Doses of CTP-543 On The Pharmacokinetics Of Single Doses of Midazolam In Healthy Subjects

A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study To Evaluate The Effect Of Multiple Doses of CTP-543 On The Pharmacokinetics Of Single Doses of Midazolam In Healthy Subjects

This is a single center, Phase 1, open-label, fixed-sequence, drug-drug interaction study to determine the effect of CTP-543 on the pharmacokinetics (PK) of midazolam in healthy adult subjects

Study Overview

• Status: Completed
• Conditions: Health Volunteers
• Intervention / Treatment: Drug: Midazolam; Drug: CTP-543

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, adult, male or female, aged 18-60
• Non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening
• If of reproductive age, willing and able to use a medically highly effective form of birth control 4 weeks prior to first dose, during the study and for 30 days following last dose of study medication
• Capable of giving informed consent and complying with study procedures

Exclusion Criteria:

• History or presence of clinically significant medical or psychiatric condition or disease
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing
• Presence or history of significant gastrointestinal, liver or kidney disease, or any other condition that is known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects
• History of prolonged QT syndrome or a QTc interval with Fridericia's correction (QTcF) > 450 msec for males or QTcF > 470 msec for females at screening visit or prior to the first dosing
• Abnormal liver function at screening
• Females who are nursing, pregnant, or planning to become pregnant while in the study, and for 30 days after last dose of study drug
• Positive results for coronavirus infection (COVID-19) at screening or check-in
• Positive drug or alcohol results at screening or check-in
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
• Participation in another clinical study within 30 days prior to, and 30 days after the first dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTP-543; Subjects will receive a single 2 mg dose of midazolam on Day 1. Starting on Day 3, 12 mg dose of CTP-543 will be administered (q12 hrs) for 14 consecutive days (up to Day 16). On Day 16, subjects will be co-administered a single 2 mg midazolam dose along with the morning dose of CTP-543. The second dose of CTP-543 will be administered as scheduled on Day 16.	Drug: Midazolam; 2 mg Day 1 and Day 16; Drug: CTP-543; 12 mg q12 hour for 14 consecutive days starting on Day 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed concentration	Day 14, 15, 16, Discharge (Day 17)
Tmax	Time to reach maximum observed concentration	Day 14, 15, 16, Discharge (Day 17)
AUC0-inf	Area under the concentration-time curve from time 0 extrapolated to infinity	Day 14, 15, 16, Discharge (Day 17)
AUC0-t	Area under the concentration-time curve from time 0 to the time of the last observed/measured non-zero concentration	Day 14, 15, 16, Discharge (Day 17)
λz	Terminal elimination rate constant	Day 14, 15, 16, Discharge (Day 17)
t1/2	Apparent terminal half-life	Day 14, 15, 16, Discharge (Day 17)
CL/F	Apparent total plasma clearance (Midazolam only)	Day 1, 2, 16, Discharge (Day 17)
Vz/F	Apparent volume of distribution (Midazolam only)	Day 1, 2, 16, Discharge (Day 17)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Safety and Tolerability following administration of CTP-543	Number of adverse events, including abnormal clinical laboratory findings, abnormal physical examinations, abnormal ECGs and abnormal vital signs tabulated for each subject	Screening (within 21 days prior to Day 1) through follow-up (approximately 7 days after last study drug administration)

Collaborators and Investigators

• Sponsor: Concert Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): July 7, 2022

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: CTP-543
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: CP543.1012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No