Phase 1
N=32
Bioequivalence Trial of Concor AM® vs Bisoprolol and Amlodipine in Chinese Participants
Healthy
Bottom Line
View on ClinicalTrials.gov: NCT03226275 ↗Enrolled (actual)
32
Serious AEs
0.0%
Results posted
Feb 2019
Primary outcome: Primary: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Bisoprolol and Amlodipine — 294; 295; 270; 275 nanogram hour per milliliter (ng*h/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Bisoprolol-Amlodipine FDC (Drug); Bisoprolol (Drug); Amlodipine (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck KGaA, Darmstadt, Germany
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Bisoprolol and Amlodipine |
294; 295; 270; 275; 205; 212 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Bisoprolol and Amlodipine |
26.1; 26.6; 20.5; 21.9; 4.17; 4.17 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of Bisoprolol and Amlodipine |
1.00; 1.00; 3.00; 3.00; 6.00; 6.00 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) of Bisoprolol and Amlodipine |
8.87; 8.84; 9.49; 8.86; 51.8; 49.7 | — |
| SECONDARY Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC 0-inf) of Bisoprolol and Amlodipine |
306; 306; 281; 287; 235; 216 | — |
| SECONDARY Extrapolated Part of Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUCextra%) of Bisoprolol and Amlodipine |
3.60; 3.24; 3.83; 3.94; 10.9; 10.8 | — |
| SECONDARY Apparent Terminal Elimination Rate Constant (λz) of Bisoprolol and Amlodipine |
0.0781; 0.0784; 0.0731; 0.0783; 0.0134; 0.0139 | — |
| SECONDARY Apparent Total Body Clearance From Plasma (CL/f) of Bisoprolol and Amlodipine |
16.4; 16.4; 17.8; 17.4; 21.3; 23.1 | — |
| SECONDARY Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Bisoprolol and Amlodipine |
209; 209; 243; 223; 1590; 1660 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, AEs Leading to Death, and AEs Leading to Discontinuation |
0; 0; 0; 0; 0; 0 | — |
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 ( 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
Data sourced from ClinicalTrials.gov (NCT03226275). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.