Bioequivalence Trial of Concor AM® vs Bisoprolol and Amlodipine in Chinese Participants
Condition: Healthy
Intervention: Bisoprolol-Amlodipine FDC; Bisoprolol; Amlodipine
Intervention description: Participants received a single oral dose of 5 milligram(mg)/5 mg bisoprolol-amlodipine FDC tablet (Concor AM®) either on Day 1 or Day 15 under fasting or fed conditions.; Participants received 5 mg bisoprolol tablet as a single oral dose either on Day 1 or Day 15 under fasting or fed conditions.; Participants received 5 mg amlodipine tablet as a single oral dose either on Day 1 or Day 15 under fasting or fed conditions.
Intervention MeSH terms: Amlodipine; Bisoprolol
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Concor AM®; Concor®; Norvasc®; Bisoprolol; Amlodipine; Bisoprolol-Amlodipine fixed dose combination; Chinese Participants

Summary:

      This is a Phase I, open-label, randomized, 2-period, 2-sequence, crossover study to
      demonstrate bioequivalence (BE) between the bisoprolol-amlodipine fixed-dose-combination
      (FDC) tablet (investigational product) and bisoprolol and amlodipine tablets administered
      concomitantly (comparators) given as a single oral dose in fasting and fed state.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Availability for the entire trial period and willingness to adhere to the protocol
             requirements as evidenced by the informed consent form (ICF) duly read, signed and
             dated by the volunteer

          -  Chinese male and female volunteer

          -  Volunteer with a body mass index greater than or equal to 18 and below 28
             kilogram/meter^2 (kg/m^2)

          -  Systolic blood pressure (in supine position) within 100 to 139 mmHg (inclusive) and
             diastolic blood pressure (in supine position) within 65 to 90 millimeter of mercury
             (mmHg) (inclusive) at Screening, during Admission to the Clinical Research Unit (CRU)
             (12 hour predose) and before each dosing

          -  Clinical laboratory values (within 1 month before screening) within the laboratory's
             stated normal range; if not within this range, they must lack clinical significance

          -  Healthy according to assessment of the medical history, Electrocardiogram, vital
             signs, physical examination,laboratory results, negative drug screening, and negative
             serology tests (except results after vaccination)

          -  Non-smoker or ex-smoker, not using any nicotine product; an ex-smoker being defined as
             someone who completely stopped smoking for at least 12 months before Day 1 of the
             trial

          -  Each participant has to be capable of understanding the trial procedures and sign the
             Informed consent form prior to their participation in the trial

          -  Participants must consent to adhere to the recommended contraceptive methods

        Exclusion Criteria:

          -  Significant history of hypersensitivity to bisoprolol, amlodipine, other
             dihydropyridines, or any related products (including excipients of the formulations)

          -  Significant history of severe hypersensitivity reactions (eg, angioedema) to any drugs

          -  Pulse rate (in supine position) less than (<) 60 beats per minute (bpm) or more than
             100 bpm at screening

          -  Presence of significant arrhythmia: QTc interval prolongation (QTc greater than 430
             milliseconds (msec), severe sinus node dysfunction, or second or third
             atrioventricular block

          -  History of low blood pressure (< 100/65 mmHg) or vegetative dystonia

          -  History or presence of peripheral arterial occlusion or Raynaud's syndrome

          -  Presence of diabetes mellitus

          -  History or presence of asthma

          -  Presence of significant gastrointestinal, liver, kidney disease, surgery, or any other
             conditions known to interfere with the absorption, distribution, metabolism, or
             excretion of drugs or known to potentiate or predispose to undesired effects

          -  Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450
             (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin,
             fluconazole, ketoconazole, diltiazem, and human immunodeficiency virus [HIV]
             antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine,
             glucocorticoids, phenytoin, rifampin, St. John's wort or other herbal medicine known
             with effect on CYP enzymes) within 28 days before Day 1 of this trial

          -  Presence or history of significant cardiovascular, pulmonary, hematologic, neurologic,
             endocrine, immunologic, or dermatological disease

          -  Presence or history of significant angina pectoris, acute myocardial infarction or ST
             segment and T wave changes other than non-clinically significant minor changes

          -  Presence or history of ventricular arrhythmia (such as ventricular tachycardia or
             ventricular fibrillation) or of congestive heart failure Acute conditions which might
             alter the renal function (eg, dehydration, severe infection)

          -  Surgery in the previous 28 days before Day 1 of this trial

          -  Any history of tuberculosis and/or prophylaxis for tuberculosis within 10 years of Day
             1 of the trial

          -  Positive results to HIV antibody, hepatitis B surface antigen (HBsAg), hepatitis C
             virus (HCV) antibody, or treponema pallidum (TP) antibody tests

          -  Donation of 50 milliliter (mL) or more of blood within 28 days before Day 1 of the
             trial; donation of 500 mL or more of blood within 56 days before Day 1 of the trial

          -  History of suicidal tendency, history of or disposition to seizures, state of
             confusion, clinically relevant psychiatric diseases

          -  Poor motivation, intellectual problems likely to limit the validity of consent to
             participate in the trial or limit the ability to comply with the protocol requirements
             or inability to cooperate adequately, inability to understand and to observe the
             instructions of the physician

          -  Maintenance therapy with any drug, or significant history of drug dependency or
             alcohol abuse (> 3 × 14 gram (g) alcohol per day, intake of excessive alcohol, acute
             or chronic use)

          -  Positive urine screening of drugs of abuse (cannabis, benzodiazepines, barbiturates,
             opiates, cocaine, and methyl amphetamine), or positive breath test of alcohol

          -  Positive pregnancy test (only for females of child-bearing potential) or females
             breast feeding a child

          -  Consumption of large quantities of methylxanthine-containing beverages (more than 600
             mg caffeine/day: 1 cup (250 mL) of coffee contains approximately 100 mg of caffeine, 1
             cup of black or green tea contains approximately 30 mg and 1 glass of cola contains
             approximately 20 mg caffeine)

          -  Volunteers who took an investigational product (in another clinical trial) by
             prescription within 2 weeks or an over-the-counter medication taken within 1 week
             before drug administration