Effect of BIA 5 1058 on Cardiac Repolarization

• Status: Completed
• Trial end date: 2018-10-05
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bial - Portela C S.A.
• Collaborator: Covance
• Treatments: Fluoroquinolones; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Zamicastat

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.

• 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.

• Use or intend to use any medications/products known to alter QT/QTc within 14 days or 5 half-lives (whichever is longer) prior to the first dose, unless deemed acceptable by the Investigator (or designee).

• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to the first dose, unless deemed acceptable by the Investigator (or designee).

• Use or intend to use any prescription medications/products including hormone replacement therapy and oral, implantable, transdermal, injectable, or intrauterine hormonal contraceptives within 14 days prior to the first dose, unless deemed acceptable by the Investigator (or designee).

• Use or intend to use any slow-release medications/products considered to still be active within 14 days prior to the first dose, unless deemed acceptable by the Investigator (or designee).

• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to the first dose, unless deemed acceptable by the Investigator (or designee).

• Use of tobacco- or nicotine-containing products within 3 months prior to Screening.

• Receipt of blood products within 2 months prior to Period 1 Check-in.

• Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.

• Vegetarians, vegans, or other medical dietary restrictions.

• Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the Investigator.

• Have previously completed or withdrawn from this study or any other study investigating BIA 5 1058, and have previously received the investigational product.

• Not able to reliably communicate with the Investigator or sub-Investigator.

• Unlikely to cooperate with the requirements of the study.

• Subjects who are study site employees or immediate family members of a study site or Sponsor employee.

• Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.