Effect of BIA 5-1058 on the Steady State Pharmacokinetics of Treprostinil

NCT04675944 | Completed Phase 1

• 2 other identifiers: BIA-51058-1062017-000245-43
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of BIA 5-1058 200 mg on the pharmacokinetic (PK) of treprostinil

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (5)

• Maximum observed plasma concentration - Cmax

  Primary Pharmacokinetic Parameters - BIA 5 1058

  Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours

• Area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable concentration - AUC0-t

  Primary Pharmacokinetic Parameters - BIA 5 1058

  Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours

• AUC from time zero extrapolated to infinity - AUC0-inf

  Primary Pharmacokinetic Parameters - BIA 5 1058

  Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours

• Maximum observed plasma concentration at steady state - Cmax,ss

  Primary Pharmacokinetic Parameters - Treprostinil

  Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours.

• AUC over the dosing interval at steady state - AUC0-τ,ss

  Primary Pharmacokinetic Parameters - Treprostinil

  Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours.

Study Arms (1)

BIA 5-1058 / treprostinil

EXPERIMENTAL

Three treatment periods separated by a washout period of at least 10 days

Drug: BIA 5-1058; Drug: treprostinil

Interventions

BIA 5-1058 DRUG

200 mg (2 x 100 mg tablets), oral route

Also known as: Zamicastat

BIA 5-1058 / treprostinil

treprostinil DRUG

1 mg (1 extended-release tablet), oral route

Also known as: Orenitram

BIA 5-1058 / treprostinil

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provided a signed and dated informed consent before any study specific procedures were conducted.
• Male and female subjects aged 18 to 45 years (both inclusive) at the Screening Visit.
• Healthy as determined by the Principal Investigator based on medical history, physical examination, clinical laboratory test results, vital signs and digital 12 lead electrocardiogram (ECG). If a vital sign or ECG assessment was outside of the reference range at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out any error.
• Non-smoker or ex-smoker for at least 3 months prior to the Screening Visit.
• Body mass index (BMI) between 18.5 and 29.9 kg/m2 (both inclusive) at the Screening Visit and on admission to each treatment period.
• Negative test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti HBc), immunoglobulin M (IgM) anti-HBc, hepatitis C virus antibody (anti HCV) and human immunodeficiency virus (HIV) (Types 1 and 2) antibodies at the Screening Visit.
• Negative screen for alcohol and drugs of abuse at the Screening Visit and on admission to each treatment period.
• Subject had to be willing and able to be confined to the clinical unit and had to adhere to the study and lifestyle restrictions.
• Contraception requirements:
• Male subjects had to use together with his female partner/spouse a highly effective contraception form of birth control in combination with a barrier method throughout the clinical study period and agreed not to father a child or to donate sperm starting at the Screening Visit and throughout the clinical study.
• Female subjects had to either be of non childbearing potential or had to use highly effective methods of contraception from at least 3 months before the Screening Visit and throughout the clinical study in combination with a barrier method.

You may not qualify if:

• Subjects who met the following criteria were considered eligible to participate/continue in the study:
• Provided a signed and dated informed consent before any study specific procedures were conducted.
• Male and female subjects aged 18 to 45 years (both inclusive) at the Screening Visit.
• Healthy as determined by the Principal Investigator based on medical history, physical examination, clinical laboratory test results, vital signs and digital 12 lead electrocardiogram (ECG). If a vital sign or ECG assessment was outside of the reference range at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out any error.
• Non-smoker or ex-smoker for at least 3 months prior to the Screening Visit.
• Body mass index (BMI) between 18.5 and 29.9 kg/m2 (both inclusive) at the Screening Visit and on admission to each treatment period.
• Negative test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti HBc), immunoglobulin M (IgM) anti-HBc, hepatitis C virus antibody (anti HCV) and human immunodeficiency virus (HIV) (Types 1 and 2) antibodies at the Screening Visit.
• Negative screen for alcohol and drugs of abuse at the Screening Visit and on admission to each treatment period.
• Subject had to be willing and able to be confined to the clinical unit and had to adhere to the study and lifestyle restrictions.
• Contraception requirements:
• Male subjects had to use together with his female partner/spouse a highly effective contraception form of birth control in combination with a barrier method throughout the clinical study period and agreed not to father a child or to donate sperm starting at the Screening Visit and throughout the clinical study.
• Female subjects had to either be of non childbearing potential or had to use highly effective methods of contraception from at least 3 months before the Screening Visit and throughout the clinical study in combination with a barrier method.
• Subjects that met any of the following criteria were not considered eligible to participate/continue in the study:
• Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue disease or disorders within 5 years before the first investigational medicinal product (IMP) administration.
• Documented coronary artery disease (any of prior myocardial infarction, positive stress test, positive nuclear perfusion study, prior coronary artery bypass graft \[CABG\] surgery or percutaneous coronary intervention, angiogram showing at least 75% stenosis in a major coronary artery), acute coronary syndrome or current symptoms of myocardial ischemia and angina.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

PAREXEL International - Early Phase Clinical Unit

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

zamicastat; treprostinil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 19, 2020
• Study Start: February 28, 2018
• Primary Completion: May 25, 2018
• Study Completion: May 25, 2018
• Last Updated: December 19, 2020

Record last verified: 2020-12

Locations

DE (1)