A Randomized, Double-blind, Placebo-controlled and Open-label, Active Controlled, 4 Period Crossover Trial to Evaluate the Effect of BIA 5 1058 on Cardiac Repolarization in Healthy Adult Males and Females Under Fed Conditions
Overview
- Phase
- Phase 1
- Intervention
- BIA 5-1058
- Conditions
- Cardiovascular Disease
- Sponsor
- Bial - Portela C S.A.
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- time-matched change from baseline in placebo-adjusted QT interval corrected for heart rate based on an individual correction method after BIA 5-1058 dosing.
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose is to evaluate the effect of single therapeutic (400 mg) and supratherapeutic (1200 mg) doses of BIA 5-1058 on the time-matched change from baseline in placebo-adjusted interval corrected (QT) for heart rate (HR)
Detailed Description
This will be a Phase 1, randomized, double-blind, placebo-controlled and open-label, active controlled, 4 period, crossover study in healthy male and female subjects under fed conditions. The study will be double blinded for BIA 5-1058 and placebo and open label for moxifloxacin. The central ECG laboratory and ECG readers will be blinded to study treatment sequence, timepoint, and subject. All subjects will receive each of the following 4 treatments: * 400 mg BIA 5 1058 * 1200 mg BIA 5 1058 * placebo * 400 mg moxifloxacin Potential subjects will be screened to assess their eligibility to enter the study between 28 and 3 days prior to the first treatment administration. For each treatment period, subjects will be admitted into the Clinical Research Unit (CRU) on Day 2 and be confined to the CRU until Discharge on Day 4. Each subject will receive a single dose of study medication on Day 1 of each treatment period. There will be a washout of at least 10 days between doses, and subjects will return to the CRU for a Follow-up visit 14 ± 2 days after Period 4 Discharge. The total duration of study participation for each subject from Screening through Follow-up visit) is anticipated to be approximately 80 days. The start of the study is defined as the date the first enrolled subject signs an Informed Consent Form (ICF). The point of enrollment occurs at the time of subject number allocation. The end of the study is defined as the date of the last subject's last assessment (scheduled or unscheduled).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Body mass index between 18.0 and 28.0 kg/m2, inclusive.
- •In good health, determined by no clinically significant findings from medical history, physical examination, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, Gilbert's syndrome\] is acceptable) at Screening or Period 1 Check-in as assessed by the Investigator (or designee).
- •No clinically significant abnormalities in 12-lead ECG rate, rhythm, or conduction at Screening or Period 1 Check-in.
- •Females will not be pregnant (negative pregnancy test at Screening and Period 1 Check in) or lactating, and females of childbearing potential and males will agree to use contraception.
- •Able to comprehend and willing to sign an ICF before any study procedure and to abide by the study restrictions.
Exclusion Criteria
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
- •Increased risk if dosed with moxifloxacin, according to the product label for moxifloxacin.
- •History of tendonitis or tendon rupture associated with treatment with quinolone antibiotics.
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- •History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
- •Subjects with alanine aminotransferase \>1.0 × the upper limit of normal (ULN) and/or aspartate aminotransferase \>1.0 × ULN and/or total bilirubin \>1.0 × ULN (isolated bilirubin \>1.0 × ULN and ≤1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%), as confirmed by subsequent repeat assessment, at Screening or Period 1 Check-in.
- •Sustained supine systolic blood pressure \>140 mmHg or \<90 mmHg or diastolic blood pressure \>95 mmHg at Screening or baseline for Period 1 unless deemed not clinically significant by the Investigator.
- •A resting ECG HR \<45 bpm or \>90 bpm.
- •An abnormal ECG indicating a second- or third-degree atrioventricular block, or one or more of the following: QRS interval \>110 ms, QTcF \<300 ms or \>450 ms, or PR interval \>220 ms. Any rhythm other than sinus rhythm that is interpreted by the Investigator to be clinically significant.
- •History of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia) or a family history of long QT syndrome or sudden death.
Arms & Interventions
Treatment Period 1
Interventions to be administered: Schema 1: 1. 400 mg BIA 5-1058 2. 1200 mg BIA 5-1058 3. Placebo 4. Moxifloxacin Schema 2: 1. 1200 mg BIA 5-1058 2. Placebo 3. 400 mg BIA 5-1058 4. Moxifloxacin
Intervention: BIA 5-1058
Treatment Period 1
Interventions to be administered: Schema 1: 1. 400 mg BIA 5-1058 2. 1200 mg BIA 5-1058 3. Placebo 4. Moxifloxacin Schema 2: 1. 1200 mg BIA 5-1058 2. Placebo 3. 400 mg BIA 5-1058 4. Moxifloxacin
Intervention: Placebo Oral Tablet
Treatment Period 1
Interventions to be administered: Schema 1: 1. 400 mg BIA 5-1058 2. 1200 mg BIA 5-1058 3. Placebo 4. Moxifloxacin Schema 2: 1. 1200 mg BIA 5-1058 2. Placebo 3. 400 mg BIA 5-1058 4. Moxifloxacin
Intervention: Moxifloxacin 400 mg
Treatment Period 2
Interventions to be administered: Schema 1 1. 1200 mg BIA 5-1058 2. Moxifloxacin 3. 400 mg BIA 5-1058 4. Placebo Schema 2: 1. Placebo 2. Moxifloxacin 3. 1200 mg BIA 5-1058 4. 400 mg BIA 5-1058
Intervention: BIA 5-1058
Treatment Period 2
Interventions to be administered: Schema 1 1. 1200 mg BIA 5-1058 2. Moxifloxacin 3. 400 mg BIA 5-1058 4. Placebo Schema 2: 1. Placebo 2. Moxifloxacin 3. 1200 mg BIA 5-1058 4. 400 mg BIA 5-1058
Intervention: Placebo Oral Tablet
Treatment Period 2
Interventions to be administered: Schema 1 1. 1200 mg BIA 5-1058 2. Moxifloxacin 3. 400 mg BIA 5-1058 4. Placebo Schema 2: 1. Placebo 2. Moxifloxacin 3. 1200 mg BIA 5-1058 4. 400 mg BIA 5-1058
Intervention: Moxifloxacin 400 mg
Treatment Period 3
Interventions to be administered: Schema 1 1. Placebo 2. 400 mg BIA 5-1058 3. Moxifloxacin 4. 1200 mg BIA 5-1058 Schema 2 1. 400 mg BIA 5-1058 2. 1200 mg BIA 5-1058 3. Moxifloxacin 4. Placebo
Intervention: BIA 5-1058
Treatment Period 3
Interventions to be administered: Schema 1 1. Placebo 2. 400 mg BIA 5-1058 3. Moxifloxacin 4. 1200 mg BIA 5-1058 Schema 2 1. 400 mg BIA 5-1058 2. 1200 mg BIA 5-1058 3. Moxifloxacin 4. Placebo
Intervention: Placebo Oral Tablet
Treatment Period 3
Interventions to be administered: Schema 1 1. Placebo 2. 400 mg BIA 5-1058 3. Moxifloxacin 4. 1200 mg BIA 5-1058 Schema 2 1. 400 mg BIA 5-1058 2. 1200 mg BIA 5-1058 3. Moxifloxacin 4. Placebo
Intervention: Moxifloxacin 400 mg
Treatment Period 4
Interventions to be administered: Schema 1 1. Moxifloxacin 2. Placebo 3. 1200 mg BIA 5-1058 4. 400 mg BIA 5-1058 Schema 2 1. Moxifloxacin 2. 400 mg BIA 5-1058 3. Placebo 4. 1200 mg BIA 5-1058
Intervention: BIA 5-1058
Treatment Period 4
Interventions to be administered: Schema 1 1. Moxifloxacin 2. Placebo 3. 1200 mg BIA 5-1058 4. 400 mg BIA 5-1058 Schema 2 1. Moxifloxacin 2. 400 mg BIA 5-1058 3. Placebo 4. 1200 mg BIA 5-1058
Intervention: Placebo Oral Tablet
Treatment Period 4
Interventions to be administered: Schema 1 1. Moxifloxacin 2. Placebo 3. 1200 mg BIA 5-1058 4. 400 mg BIA 5-1058 Schema 2 1. Moxifloxacin 2. 400 mg BIA 5-1058 3. Placebo 4. 1200 mg BIA 5-1058
Intervention: Moxifloxacin 400 mg
Outcomes
Primary Outcomes
time-matched change from baseline in placebo-adjusted QT interval corrected for heart rate based on an individual correction method after BIA 5-1058 dosing.
Time Frame: Day 1 at -1.25, -1, and -0.75 hours predose, Day -1 (baseline) at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 23 hours postdose.
In each treatment period, continuous 12-lead digital ECG recording will be performed by Holter monitor for at least 24 hours prior to dose until approximately 24 hours postdose.
Secondary Outcomes
- QT interval corrected for heart rate based on the Fridericia correction (QTcF)(Day 1 at -1.25, -1, and -0.75 hours predose, Day -1 (baseline) at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 23 hours postdose.)