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

NCT01135680 | Completed Phase 1

• 1 other identifier: HPN-100-010
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

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).

Conditions

Drug Toxicity

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

• 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

• 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

• 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

Study Arms (2)

Arm 1

PLACEBO COMPARATOR

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

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

Arm 2

PLACEBO COMPARATOR

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

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

Interventions

HPN-100 DRUG

single oral dose of 9 mL HPN-100 given via syringes 3 times daily for 3 days

Arm 1

HPN-100 or Placebo DRUG

single oral dose of 12 mL HPN-100 given via syringes 3 times daily for 3 days

Arm 1

Placebo DRUG

single oral (by mouth) dose of 9 mL placebo given via syringes 3 times daily for 3 days

Arm 2

Moxifloxacin DRUG

single oral 400-mg dose on study Day 3

Arm 2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

Covance Clinical Pharmacology, Inc.

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Interventions

glycerol phenylbutyrate; Moxifloxacin

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2010
• First Posted: June 3, 2010
• Study Start: May 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (1)