Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of CTP-543

A Phase 1 Study to Assess the Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics of CTP-543 (Deuruxolitinib Phosphate)

This is an open-label, single-dose, single-period, parallel group designed study to determine the effect of mild and moderate hepatic impairment on the pharmacokinetics (PK) of CTP-543 and its major metabolites following administration of a single 12 mg oral dose of CTP-543.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: CTP-543

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult males or females aged 18-75
• Body mass index (BMI) ≥ 18.0 and ≤ 42.0 kg/m2 at the time of screening
• If of reproductive age, willing and able to use a medically highly effective form of birth control 30 days 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

Additional Inclusion Criteria for Subjects with Hepatic Impairment:

• For moderate hepatic impairment, the subject must have a Child-Pugh score of 7 to 9 at the time of screening. For mild hepatic impairment, the subject must have a Child- Pugh score of 5 to 6 at the time of screening.
• No clinically significant change in disease status within the last 30 days before screening
• The subject must have a condition consistent with hepatic impairment and associated symptoms, but otherwise be determined to be healthy in the opinion of the Investigator
• If diabetic, the subject must have the disease controlled

Exclusion Criteria:

• History of any clinically significant medical condition, psychiatric disease, social condition, or illness that might confound the results of the study or poses an additional risk to the subject by their participation in the study
• Known history of any GI surgery or any condition possibly affecting drug absorption
• History of prolonged QT syndrome or a QTc interval with Fridericia's correction (QTcF) > 470 msec for males or QTcF > 480 msec for females at Screening visit.
• Females who are nursing or pregnant prior to drug administration
• Positive for human immunodeficiency virus (HIV)
• Positive results for coronavirus infection (COVID-19) at screening or check-in
• Positive drugs of abuse or alcohol results at screening or check in (Day -1)

Additional Exclusion Criteria for Subjects with Hepatic Impairment:

• History or current diagnosis of uncontrolled or significant cardiac disease
• Gilbert's syndrome, liver transplant, Wilson's disease, autoimmune liver disease, esophageal variceal bleeding within 3 months prior to screening
• Previous diagnosis of hepatocellular carcinoma
• Acute or exacerbating hepatitis, fluctuating or rapidly deteriorating hepatic function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTP-543 Treatment - Mild Hepatic Impairment	Drug: CTP-543; Single 12 mg oral dose administered on Day 1
Experimental: CTP-543 Treatment - Moderate Hepatic Impairment	Drug: CTP-543; Single 12 mg oral dose administered on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single dose PK exposure: Maximum observed concentration (Cmax)	Maximum concentration, obtained directly from the observed concentration versus time data.	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 36, 48 hours post-dose
Single dose PK exposure: Area Under the Concentration-Time Curve from time zero to the time of the last observed/measured non-zero concentration (AUC0-t)	Area under the concentration-time curve from time zero (pre-dose) to time of last measurable concentration (calculated by linear-log trapezoidal summation)	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 36, 48 hours post-dose
Single dose PK exposure: Area Under the Concentration-Time Curve from time 0 extrapolated to infinity (AUC0-inf)	Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinity, calculated by linear-log trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration divided by the elimination rate constant	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 36, 48 hours post-dose

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 (7 to 10 days after the final administration of study drug)

Collaborators and Investigators

• Sponsor: Concert Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): September 15, 2022
• Study Completion (Actual): September 21, 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): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: CTP-543
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CP543.1013

Drug and device information, study documents

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