Effect of BIA 5 1058 on Cardiac Repolarization

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03489005
• Date of registration: 29/03/2018
• Prospective Registration: Yes
• Primary sponsor: Bial - Portela C S.A.
• Public title: Effect of BIA 5 1058 on Cardiac Repolarization
• Scientific title: 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
• Date of first enrolment: April 9, 2018
• Target sample size: 49
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03489005
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Heart Failure

Cardiovascular Disease

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Moxifloxacin 400 mg

Drug: Placebo Oral Tablet

Drug: BIA 5-1058

Primary Outcome(s)

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 24 hours postdose.]

Secondary Outcome(s)

QT interval corrected for heart rate based on the Fridericia correction (QTcF) [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 24 hours postdose.]

Secondary ID(s)

2017-001682-25

BIA-51058-115

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Covance