Study of Lumacaftor in Combination With Ivacaftor in Subjects With Moderate Hepatic Impairment and Healthy Subjects

A Phase 1, Open Label Study to Assess the Pharmacokinetics and Safety of Multiple Doses of Lumacaftor in Combination With Ivacaftor in Subjects With Moderate Hepatic Impairment and in Matched Healthy Subjects

This study is designed to evaluate the pharmacokinetics (PK) and safety of multiple doses of lumacaftor in combination with ivacaftor in subjects with moderate hepatic impairment.

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: lumacaftor 200 mg q12h + ivacaftor 250 mg q12h

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czech Republic
  • Praha, Czech Republic
• Slovakia
  • Bratislava, Slovakia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Group A: Subjects with Moderate Hepatic Impairment

• Male and female 18 to 65 years of age (inclusive)
• Satisfy the criteria for moderate hepatic impairment defined as a Child Pugh total score of 7 to 9 (Child Pugh Class B) at the Screening Visit
• Willing and able to comply with schedule visits, treatment, laboratory tests, and contraceptive guidelines.

Group B: Healthy subjects

• Male and female 18 to 65 years of age (inclusive)
• Healthy subjects with no clinically relevant abnormalities identified by a detailed medical history, complete physical examination, including blood pressure and pulse rate measurement, standard 12-lead ECG, and clinical laboratory tests
• Willing and able to comply with schedule visits, treatment, laboratory tests, contraceptive guidelines and other study procedures

Exclusion Criteria:

Group A: Subjects with Moderate Hepatic Impairment

• History of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject
• Have fluctuating or rapidly deteriorating hepatic function by history or as indicated by significant variations in or worsening of clinical and/or laboratory signs of hepatic impairment within 6 months before the Screening Visit
• Other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver
• Severe hepatic encephalopathy
• Type 1 diabetes mellitus or evidence of poorly controlled type 2 diabetes
• Hepatocellular carcinoma, HIV, hepatitis B/C
• Significant renal dysfunction
• Solid organ or bone marrow transplantation
• History of regular alcohol consumption, drug abuse or regular smoking

Group B: Healthy subjects

• History of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject
• History of regular alcohol consumption, drug abuse or regular smoking

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Approximately 12 subjects (male and female) with moderate hepatic impairment	Drug: lumacaftor 200 mg q12h + ivacaftor 250 mg q12h
Experimental: Group B; Approximately 12 healthy subjects (male and female)	Drug: lumacaftor 200 mg q12h + ivacaftor 250 mg q12h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Lumacaftor pharmacokinetic parameters, including Cmax, tmax, AUC, Vd, CL/F	16 days
Ivacaftor pharmacokinetic parameters, including Cmax, tmax, AUC, Vd, CL/F	16 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Lumacaftor metabolites pharmacokinetic parameters, including Cmax and AUC	16 days
Ivacaftor metabolites pharmacokinetic parameters including Cmax, tmax, AUC	16 days
Safety and tolerability as mentioned by adverse events, clinical laboratory values, standard electrocardiograms, Vital signs and pulse oximetry	21 days

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: June 20, 2013
• First Submitted That Met QC Criteria: June 26, 2013
• First Posted (Estimate): June 27, 2013

Study Record Updates

• Last Update Posted (Estimate): November 19, 2013
• Last Update Submitted That Met QC Criteria: November 18, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: pharmacokinetics, hepatic impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX13-809-010