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

Phase 1

Completed

• Conditions: Healthy; Hepatic Impairment
• Interventions: Drug: lumacaftor 200 mg q12h + ivacaftor 250 mg q12h

• Registration Number: NCT01888393
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-06-20
• Study First Submitted QC: 2013-06-26
• Study First Posted: 2013-06-27
• Status Verified: 2013-11
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Last Update Submitted: 2013-11-18
• Last Update Posted: 2013-11-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	lumacaftor 200 mg q12h + ivacaftor 250 mg q12h	Approximately 12 subjects (male and female) with moderate hepatic impairment
Group B	lumacaftor 200 mg q12h + ivacaftor 250 mg q12h	Approximately 12 healthy subjects (male and female)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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