Double-Blind Randomized Crossover Trial to Access Electrocardiogram Effects of HPN-100
Phase 1
Completed
- Conditions
- Drug Toxicity
- Interventions
- Registration Number
- NCT01135680
- Lead Sponsor
- Amgen
- Brief Summary
Arm 1:
Primary Objective:
• To determine the safety and tolerability of multiple ascending, supratherapeutic doses of HPN-100.
Arm 2:
Primary Objective:
• To assess the effects of steady-state levels of HPN-100 metabolites (4 phenylbutyric acid \[PBA\], phenylacetic acid \[PAA\], and phenylacetylglutamine \[PAGN\]) on 12-lead electrocardiogram (ECG) parameters in healthy male and female subjects with the primary endpoint being the time-matched change from baseline in the QT interval corrected for heart rate (HR) based on an individual correction method (QTcI).
- Detailed Description
Assess the effects of steady-state levels of HPN-100 metabolites (4-phenylbutryic acid (PBA), phenylacetic acid (PAA), and phenylacetylglutamine (PAGN) on 12-lead electrocardiogram (ECG) parameters in health male and female subjects with the primary endpoint being the time-matched change from baseline in the QT interval corrected for heart rate(HR) based on an individual correction method (QTcl).
Study acquired from Horizon in 2024.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 98
Inclusion Criteria
- Must be in good health
- Negative hepatitis panel and negative HIV antibody screens
- Females must be non-pregnant, non-lactating, and either postmenopausal or agree to to use adequate contraceptive methods throughout the study
- Males must either be sterile or willing to use adequate contraceptive methods throughout the study
- Willing and able to comply with all trial requirements
- Able to comprehend and willing to sign an Informed Consent Form (ICF)
Exclusion Criteria
- History or clinical manifestations of significant allergic, metabolic, hepatic, renal, endocrine, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders
- History of hypersensitivity or allergies to any drug compound
- History of stomach or intestinal surgery or resection
- History or presence of an abnormal ECG
- History of alcoholism or drug addiction within 1 year
- Use of any tobacco-containing or nicotine-containing products within 3 months
- Participated in any other clinical trial of an investigational drug (or a medical device) within 30 days
- Use of any prescription medications/products other than contraceptives within 14 days
- Use of any over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days
- Test positive for drug(s) of abuse, ethanol, or cotinine
- Have donated blood or blood components within 30 days
- Have received blood products within 2 months
- Have a history of unexplained syncope
- Have a family history of unexplained sudden death
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm 1 HPN-100 Cohort A: 9 mL HPN-100 or placebo Cohort B: 12 mL HPN-100 placebo Arm 1 HPN-100 or Placebo Cohort A: 9 mL HPN-100 or placebo Cohort B: 12 mL HPN-100 placebo Arm 2 Placebo This study requires 4 periods. In each of the periods you will receive one of the dose groups listed below. At the completion of the study you will have participated in all 4 dose groups. The order in which you participate in each dose group will be randomly assigned. Dose Group A: 9 mL placebo via oral syringe 3 times daily for 3 days Dose Group B: single oral dose of 400 mg moxifloxacin on study Day 3 Dose Group C: 6 mL HPN-100 and 3 mL placebo via oral syringe 3 times daily for 3 days Dose Group D: 9 mL HPN-100 via oral syringe 3 times daily for 3 days Arm 2 HPN-100 This study requires 4 periods. In each of the periods you will receive one of the dose groups listed below. At the completion of the study you will have participated in all 4 dose groups. The order in which you participate in each dose group will be randomly assigned. Dose Group A: 9 mL placebo via oral syringe 3 times daily for 3 days Dose Group B: single oral dose of 400 mg moxifloxacin on study Day 3 Dose Group C: 6 mL HPN-100 and 3 mL placebo via oral syringe 3 times daily for 3 days Dose Group D: 9 mL HPN-100 via oral syringe 3 times daily for 3 days Arm 2 Moxifloxacin This study requires 4 periods. In each of the periods you will receive one of the dose groups listed below. At the completion of the study you will have participated in all 4 dose groups. The order in which you participate in each dose group will be randomly assigned. Dose Group A: 9 mL placebo via oral syringe 3 times daily for 3 days Dose Group B: single oral dose of 400 mg moxifloxacin on study Day 3 Dose Group C: 6 mL HPN-100 and 3 mL placebo via oral syringe 3 times daily for 3 days Dose Group D: 9 mL HPN-100 via oral syringe 3 times daily for 3 days
- Primary Outcome Measures
Name Time Method Safety and tolerability as measured by the rate and severity of adverse events in each treatment group. 3-day treatment period Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
- Secondary Outcome Measures
Name Time Method Correlate time-matched QTcI change from baseline and serum levels of PBA, PAA, and PAGN drawn on Day 1, Day 2, Day 3, and Day 4 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments Number and severity of adverse events in each treatment group. 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments Correlate time-matched ECG waveform changes to steady-state levels of HPN-100 by using QTcB and QTcF formulas to assess ECG morphologic changes. 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments Gender differences in metabolism of HPN-100 as measured by time-matched serum levels of HTN-100, PBA, PAA, and PAGN via samples drawn on Day 1, Day 2, Day 3, and Day 4. 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
Trial Locations
- Locations (1)
Covance Clinical Pharmacology, Inc.
🇺🇸Madison, Wisconsin, United States