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

Drug Toxicity Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01135680
• Other study ID #: HPN-100-010
• Status: Completed
• Phase: Phase 1
• First received: May 31, 2010
• Last updated: January 13, 2017
• Start date: May 2010
• Est. completion date: September 2010

Study information

• Verified date: June 2015
• Source: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Toxicity
• Drug-Related Side Effects and Adverse Reactions

Intervention

Drug:
• HPN-100
single oral dose of 9 mL HPN-100 given via syringes 3 times daily for 3 days
• HPN-100 or Placebo
single oral dose of 12 mL HPN-100 given via syringes 3 times daily for 3 days
• Placebo
single oral (by mouth) dose of 9 mL placebo given via syringes 3 times daily for 3 days
• Moxifloxacin
single oral 400-mg dose on study Day 3
• HPN-100
single oral dose of 6 mL HPN-100 and 3 mL placebo given via syringes 3 times daily for 3 days
• HPN-100
single oral dose of 9 mL HPN-100 given via syringes 3 times daily for 3 days

Locations

Country	Name	City	State
United States	Covance Clinical Pharmacology, Inc.	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Horizon Pharma Ireland, Ltd., Dublin Ireland

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability as measured by the rate and severity of adverse events in each treatment group.		3-day treatment period
Primary	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	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
Secondary	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
Secondary	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
Secondary	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