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

Primary Purpose

Drug Toxicity

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

HPN-100

HPN-100 or Placebo

Placebo

Moxifloxacin

HPN-100

About this trial

This is an interventional diagnostic trial for Drug Toxicity

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts 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

Sites / Locations

Covance Clinical Pharmacology, Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Arm Label

Arm 1

Arm 2

Arm Description

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

Outcomes

Primary Outcome Measures

Safety and tolerability as measured by the rate and severity of adverse events in each treatment group.

Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN

Secondary Outcome Measures

Correlate time-matched ECG waveform changes to steady-state levels of HPN-100 by using QTcB and QTcF formulas to assess ECG morphologic changes.

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

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.

Number and severity of adverse events in each treatment group.

Full Information

NCT ID

NCT01135680

First Posted

May 31, 2010

Last Updated

January 13, 2017

Sponsor

Horizon Pharma Ireland, Ltd., Dublin Ireland

1. Study Identification

Unique Protocol Identification Number

NCT01135680

Brief Title

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

Official Title

Double-Blind Randomized Placebo-Control Trial to Evaluate Electrocardiogram Effects of HPN-100 as Defined by Clinical and Supratherapeutic Dose in Healthy Men and Women

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

September 2010 (Actual)

Study Completion Date

September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Horizon Pharma Ireland, Ltd., Dublin Ireland

4. Oversight

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Drug Toxicity

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

98 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Arm 2

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

HPN-100

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

HPN-100 or Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Moxifloxacin

Intervention Description

single oral 400-mg dose on study Day 3

Intervention Type

Drug

Intervention Name(s)

HPN-100

Intervention Description

single oral dose of 6 mL HPN-100 and 3 mL placebo given via syringes 3 times daily for 3 days

Intervention Type

Drug

Intervention Name(s)

HPN-100

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety and tolerability as measured by the rate and severity of adverse events in each treatment group.

Time Frame

3-day treatment period

Title

Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN

Time Frame