A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study to Evaluate the Effect of Multiple Doses of Fluconazole, a CYP3A4 and CYP2C9 Inhibitor, on the Pharmacokinetics of CTP-543 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- CTP-543
- Conditions
- Health Volunteers
- Sponsor
- Concert Pharmaceuticals
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Tmax
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
A single center, Phase 1, open-label, fixed-sequence, drug-drug interaction study to evaluate the effect of multiple doses of Fluconazole, a CYP3A4 and CYP2C9 inhibitor, on the pharmacokinetics (PK) of CTP-543 in healthy subjects
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, adult, male or female, aged 18-60 inclusive
- •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.
- •Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol
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
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds
- •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)
Arms & Interventions
CTP-543 and Fluconazole Treatment
On Day 1, each subject will receive a single oral dose of 12 mg CTP-543. Following a washout on Day 2, each subject will receive an oral dose of 200 mg fluconazole once daily on Days 3 through to Day 8. On Day 7, approximately 1 hour after the 200 mg dose of fluconazole, each subject will receive a single oral dose of 12 mg CTP-543.
Intervention: CTP-543
CTP-543 and Fluconazole Treatment
On Day 1, each subject will receive a single oral dose of 12 mg CTP-543. Following a washout on Day 2, each subject will receive an oral dose of 200 mg fluconazole once daily on Days 3 through to Day 8. On Day 7, approximately 1 hour after the 200 mg dose of fluconazole, each subject will receive a single oral dose of 12 mg CTP-543.
Intervention: Fluconazole
Outcomes
Primary Outcomes
Tmax
Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Time to reach maximum observed concentration
AUC0-inf
Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Area under the concentration-time curve from time 0 extrapolated to infinity
t1/2
Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Apparent terminal half-life
Cmax
Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Maximum observed concentration
λz
Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Terminal elimination rate constant
AUC0-tlast
Time Frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Area under the concentration-time curve from time 0 to the time of the last observed/measured non-zero concentration
Secondary Outcomes
- Assessment of Safety and Tolerability following administration of CTP-543(Continuous from screening (within 21 days prior to Day 1) through Discharge (approximately 7 days after last study drug administration))