Clinical trial NCT01135680: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Toxicity
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-06-03
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

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).

Study acquired from Horizon in 2024.

Eligibility 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

Primary outcomes:
measure: Safety and tolerability as measured by the rate and severity of adverse events in each treatment group.
timeFrame: 3-day treatment period
measure: Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN
timeFrame: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
Secondary outcomes:
measure: Correlate time-matched ECG waveform changes to steady-state levels of HPN-100 by using QTcB and QTcF formulas to assess ECG morphologic changes.
timeFrame: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
measure: 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
timeFrame: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
measure: 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.
timeFrame: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
measure: Number and severity of adverse events in each treatment group.
timeFrame: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Pharmacology, Inc.
state: Wisconsin
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: