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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Hepatic Impairment, Healthy

Intervention / Treatment
-----------------
* Drug: lumacaftor 200 mg q12h + ivacaftor 250 mg q12h


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pharmacokinetics, hepatic impairment