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Phase 1, QT/QTC Interval Study in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT01910415
Recruitment Status : Completed
First Posted : July 29, 2013
Last Update Posted : August 11, 2014
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Brief Summary:
This study is designed to evaluate the effect of multiple doses of lumacaftor in combination with ivacaftor on cardiac repolarization, as detected by QT/QTc interval corrected for heart rate in healthy subjects.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Lumacaftor Drug: Lumacaftor Placebo Drug: Ivacaftor Drug: Ivacaftor Placebo Drug: moxifloxacin hydrochloride Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Placebo and Active Controlled, Double-Blind, Parallel, Electrocardiogram Study to Evaluate the Effect of Lumacaftor in Combination With Ivacaftor on the QT/QTc Interval in Healthy Subjects
Study Start Date : June 2013
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Ivacaftor

Arm Intervention/treatment
Experimental: Part A

Will consist of up to 4 cohorts with subjects receiving lumacaftor or placebo for 7 days.

Cohort 1: 600 mg lumacaftor once a day Cohort 2: 1000 mg lumacaftor once a day Cohort 3: 1200 mg lumacaftor once a day

Drug: Lumacaftor
Other Name: VX-809

Drug: Lumacaftor Placebo
Experimental: Part B

Will consist of 3 cohorts. All cohorts will be dosed in parallel. Cohort A will receive 600 mg Lumacaftor once a day plus 250 mg Ivacaftor twice a day for 7 days. From day 8-14 subjects will receive a supratherapeutic dose of Lumacaftor (TBD) plus 450 mg Ivacaftor twice a day.

Cohort B will receive lumacaftor and ivacaftor matching placebo for 14 days Cohort C will receive a single dose of 400 mg moxifloxacin on day 14

Drug: Lumacaftor
Other Name: VX-809

Drug: Lumacaftor Placebo
Drug: Ivacaftor
Other Name: VX-770

Drug: Ivacaftor Placebo
Drug: moxifloxacin hydrochloride



Primary Outcome Measures :
  1. (Part A) Safety and tolerability of lumacaftor as measured by standard 12-lead ECGs, adverse events (AEs), vital signs, spirometry, and clinically significant laboratory assessments [ Time Frame: 7 days ]
  2. (Part B) Time matched, baseline-adjusted change in QTcF intervals obtained from a continuous ECG recording over a 24 hour interval after administration of a therapeutic and supratherapeutic dose of lumacaftor in combination with ivacaftor [ Time Frame: 7 days ]

Secondary Outcome Measures :
  1. (Part A) PK parameters of lumacaftor and M28-lumacaftor in plasma including Cmax and AUC [ Time Frame: up to 11 days ]
  2. (Part B) Time-matched, baseline-adjusted QTcF intervals obtained after a single 400-mg dose of moxifloxacin [ Time Frame: up to 14 days ]
  3. (Part B) Time-matched, baseline-adjusted non-QT interval parameters obtained from a continuous ECG recording over a 24-hour interval [ Time Frame: up to 14 days ]
  4. (Part B) PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor including Cmax and AUC [ Time Frame: up to 15 days ]
  5. (Part B) PK/PD relationship between plasma concentration and QT/QTc interval [ Time Frame: up to 14 days ]
  6. (Part B) Safety and tolerability of lumacaftor in combination with ivacaftor as measured by standard 12-lead ECGs, AEs, vital signs, and clinical significant laboratory results [ Time Frame: up to 24 days ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects must be willing and able to comply with scheduled visits, treatment plan, lifestyle guidelines, laboratory tests, contraceptive guidelines, and other study procedures.
  • Subjects must be healthy, as defined by no clinically relevant abnormalities identified by a detailed medical history, physical examination, including blood pressure and pulse rate measurement, and 12 lead ECG.
  • Subjects must weigh >50kg

Exclusion Criteria:

  • Abnormal renal function at Screening
  • Plasma donation within 7 days before first study drug dose or blood donation of 1 pint (500mL) within 56 days before first study drug dose
  • Positively screen for Hepatitis B, Hepatitis C, HIV
  • Known hypersensitivity or prior adverse reaction to moxifloxacin or other quinolones
  • Any condition possibly affecting drug absorption (e.g., gastrectomy, or other gastrointestinal tract surgery, except appendectomy or cholecystectomy or polypectomy) or regular use of acid-lowering therapies (H2 blockers, proton pump inhibitors, and antacids).
  • Female subjects who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last study drug dose and female subjects of childbearing potential who are unwilling or unable to follow the contraceptive guidelines from at least 14 days before the first study drug dose.
  • Male subject who has a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last study drug dose; male subjects who are unwilling or unable to follow the contraceptive guidelines

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01910415


Locations
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Netherlands
Zuidlaren, Netherlands
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated

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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01910415     History of Changes
Other Study ID Numbers: VX12-809-008
First Posted: July 29, 2013    Key Record Dates
Last Update Posted: August 11, 2014
Last Verified: February 2014
Additional relevant MeSH terms:
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Cystic Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Ivacaftor
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Chloride Channel Agonists
Membrane Transport Modulators