Effect of BIA 5 1058 on Cardiac Repolarization

NCT03489005 | Completed Phase 1

• 2 other identifiers: BIA-51058-1152017-001682-25
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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)

Conditions

Cardiovascular Disease; Pulmonary Arterial Hypertension; Heart Failure

Keywords

BIA 5-1058; Pulmonary arterial hypertension; Heart failure; Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

Secondary Outcomes (1)

• 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.

Study Arms (4)

Treatment Period 1

OTHER

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

Drug: BIA 5-1058; Drug: Placebo Oral Tablet; Drug: Moxifloxacin 400 mg

Treatment Period 2

OTHER

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

Drug: BIA 5-1058; Drug: Placebo Oral Tablet; Drug: Moxifloxacin 400 mg

Treatment Period 3

OTHER

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

Drug: BIA 5-1058; Drug: Placebo Oral Tablet; Drug: Moxifloxacin 400 mg

Treatment Period 4

OTHER

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

Drug: BIA 5-1058; Drug: Placebo Oral Tablet; Drug: Moxifloxacin 400 mg

Interventions

BIA 5-1058 DRUG

Subjects will receive BIA 5-1058 tablets (containing 100 mg) as single, oral doses 30 minutes after the start of a moderate mealas follows: * 400 mg BIA 5 1058, as 4 × 100 mg tablets and 8 placebo tablets * 1200 mg BIA 5 1058, as 12 × 100 mg tablets

Also known as: Zamicastat

Treatment Period 1; Treatment Period 2; Treatment Period 3; Treatment Period 4

Placebo Oral Tablet DRUG

Matching placebo tablets administered as follows: \- placebo, as 12 × 0-mg tablets

Treatment Period 1; Treatment Period 2; Treatment Period 3; Treatment Period 4

Moxifloxacin 400 mg DRUG

Administered as follows: \- 400 mg moxifloxacin, as 1 × 400-mg tablet

Treatment Period 1; Treatment Period 2; Treatment Period 3; Treatment Period 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• History of clinically significant alcoholism or drug/chemical abuse.
• Alcohol consumption of \>28 units per week for males and \>21 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
• Positive alcohol breath test result, positive urine cotinine test, or positive urine drug screen (confirmed by repeat) at Screening or Period 1 Check-in.
• Positive hepatitis panel and/or positive human immunodeficiency virus test. Subjects whose results are compatible with prior immunization may be included at the discretion of the Investigator.
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to the first dose.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit Ltd.

Leeds, LS29LH, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Pulmonary Arterial Hypertension; Heart Failure

Interventions

zamicastat; Moxifloxacin

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Heart Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 5, 2018
• Study Start: April 9, 2018
• Primary Completion: October 5, 2018
• Study Completion: October 5, 2018
• Last Updated: December 31, 2020

Record last verified: 2019-10

Locations

GB (1)