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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01135680
First Posted: June 3, 2010
Last Update Posted: January 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland
  Purpose

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).


Condition Intervention Phase
Drug Toxicity Drug: HPN-100 Drug: HPN-100 or Placebo Drug: Placebo Drug: Moxifloxacin Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:

Primary Outcome Measures:
  • Safety and tolerability as measured by the rate and severity of adverse events in each treatment group. [ Time Frame: 3-day treatment period ]
  • Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN [ Time Frame: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments ]

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. [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments ]

Enrollment: 98
Study Start Date: May 2010
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1

Cohort A: 9 mL HPN-100 or placebo

Cohort B: 12 mL HPN-100 placebo

Drug: HPN-100
single oral dose of 9 mL HPN-100 given via syringes 3 times daily for 3 days
Drug: HPN-100 or Placebo
single oral dose of 12 mL HPN-100 given via syringes 3 times daily for 3 days
Placebo Comparator: Arm 2

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

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).
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01135680


Locations
United States, Wisconsin
Covance Clinical Pharmacology, Inc.
Madison, Wisconsin, United States, 53704
Sponsors and Collaborators
Horizon Pharma Ireland, Ltd., Dublin Ireland
  More Information

Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT01135680     History of Changes
Other Study ID Numbers: HPN-100-010
First Submitted: May 31, 2010
First Posted: June 3, 2010
Last Update Posted: January 16, 2017
Last Verified: June 2015

Additional relevant MeSH terms:
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Glycerol
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Cryoprotective Agents
Protective Agents


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