Double-Blind Randomized Crossover Trial to Access Electrocardiogram Effects of HPN-100

Amgen

Status and phase: Completed; Phase 1

Conditions: Drug Toxicity

Treatments: Drug: HPN-100; Drug: Placebo; Drug: Moxifloxacin; Drug: HPN-100 or Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01135680

HPN-100-010

Details and patient eligibility

About

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).

Full 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.

Enrollment: 98 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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98 participants in 2 patient groups, including a placebo group

Arm 1

Placebo Comparator group

Description:

Cohort A: 9 mL HPN-100 or placebo Cohort B: 12 mL HPN-100 placebo

Treatment:

Drug: HPN-100 or Placebo

Drug: HPN-100

Drug: HPN-100

Drug: HPN-100

Arm 2

Placebo Comparator group

Description:

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

Treatment:

Drug: Moxifloxacin

Drug: HPN-100

Drug: Placebo

Drug: HPN-100

Drug: HPN-100