Clinical trial NCT01888393: Study of Lumacaftor in Combination With Ivacaftor in Subjects With Moderate Hepatic Impairment and Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy
Keywords: pharmacokinetics, hepatic impairment
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2013-06-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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.


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

Primary outcomes:
measure: Lumacaftor pharmacokinetic parameters, including Cmax, tmax, AUC, Vd, CL/F
timeFrame: 16 days
measure: Ivacaftor pharmacokinetic parameters, including Cmax, tmax, AUC, Vd, CL/F
timeFrame: 16 days
Secondary outcomes:
measure: Lumacaftor metabolites pharmacokinetic parameters, including Cmax and AUC
timeFrame: 16 days
measure: Ivacaftor metabolites pharmacokinetic parameters including Cmax, tmax, AUC
timeFrame: 16 days
measure: Safety and tolerability as mentioned by adverse events, clinical laboratory values, standard electrocardiograms, Vital signs and pulse oximetry
timeFrame: 21 days
Other outcomes:
Locations:
city: Praha
country: Czech Republic
city: Bratislava
country: Slovakia
Study officials:
References: