Clinical trial NCT05083949: A Study in Healthy Humans to Assess the Relative Bioavailability of One Fixed-dose Combination Tablet Empagliflozin/Metformin Versus Jardiance® Tablet and Glifage® Tablet Administered Together
Official title: Relative Bioavailability of Empagliflozin/Metformin Fixed-dose Combination - Empagliflozin 12.5 mg + Metformin 850mg (Boehringer Ingelheim) Coated Tablet Versus Jardiance® 10mg (Reference 1: Boehringer Ingelheim) Coated Tablet and Glifage® 850mg (Reference 2: Merck S / A. ) Coated Tablet, Administered Together in Healthy Male and Female Subjects Under Fed Conditions: an Open-label, Randomised, Single-dose, Two-way Crossover Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-10-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This trial is to establish bioequivalence of the fixed dose combination (FDC) tablets (containing 12.5 mg empagliflozin/850 mg metformin) (Test, T) compared with the single tablets (10 mg empagliflozin and Glifage® 850 mg tablets) (Reference, R).


Eligibility criteria: Inclusion criteria:

* Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
* Age of at least 18 (inclusive) to 50 years (inclusive)
* Body mass index (BMI) of 18.5 to 29.9 weight divided by height squared (kg/m2) (inclusive)
* Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
* Male subjects, or female subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:
* Use of adequate contraception, e.g. any of the following methods plus condom:

  * implants, injectables, combined oral or vaginal contraceptives, intrauterine device
  * Sexually abstinent
  * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  * Surgically sterilised (including hysterectomy)

Exclusion Criteria:

* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
* Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
* Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
* History of relevant orthostatic hypotension, fainting spells, or blackouts
* Chronic or relevant acute infections
* Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause time from the start of the Q wave to the end of the T wave (QT) / corrected QT (QTc) interval prolongation)
* Smoker (more than 5 cigarettes or 1 cigar or 1 pipe per day)
* Detection or indeterminate / inconclusive result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Coronavirus ribonucleic acid (RNA) in the quantitative real-time polymerase chain reaction (RT-qPCR) exam performed on the day before the admission of each period;
* The research participant presents symptoms of coronavirus disease 2019 (COVID-19) infection (even if the result is "undetected" in the RT-PCR exam for COVID-19)
* Further exclusion criteria apply

Primary outcomes:
measure: Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
timeFrame: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Dose-normalized Maximum Measured Concentration of Empagliflozin (Cmax)
timeFrame: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Maximum Measured Concentration of Metformin (Cmax)
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Secondary outcomes:
measure: Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ )
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Time From Last Dosing to the Maximum Measured Concentration of Empagliflozin in Plasma (Tmax)
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Time From Last Dosing to the Maximum Measured Concentration of Metformin in Plasma (Tmax)
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Percentage (%) of the AUC of Empagliflozin That Has Been Derived After Extrapolation
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Percentage (%) of the AUC of Metformin That Has Been Derived After Extrapolation
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Terminal Half-life of Empagliflozin in Plasma (t1/2)
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Terminal Half-life of Metformin in Plasma (t1/2)
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Elimination Rate Constant (Kel) for Empagliflozin
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
measure: Elimination Rate Constant (Kel) for Metformin
timeFrame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Other outcomes:
Locations:
city: Goiânia
country: Brazil
facility: Instituto de Ciências Farmacêuticas de Estudos e Pesquisas - ICF
Study officials:
References: