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Phase 1 Completed N=32 Randomized Treatment

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

Healthy
Source: ClinicalTrials.gov NCT05083949 ↗
Enrolled (actual)
32
Serious AEs
0.0%
Results posted
Jul 2023
Primary outcomePrimary: 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) — 117.15; 116.65 (h*ng/mL)/mg — p=0.7792

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).

Outcome Measures

OutcomeResultp-value
PRIMARY
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)
117.15; 116.65 0.7792
PRIMARY
Dose-normalized Maximum Measured Concentration of Empagliflozin (Cmax)
13.42; 13.60 0.6493
PRIMARY
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
10299.45; 10467.41 0.4710
PRIMARY
Maximum Measured Concentration of Metformin (Cmax)
1333.58; 1308.39 0.4251
SECONDARY
Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ )
118.25; 117.64 0.7379
SECONDARY
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
10440.79; 10570.45 0.5895
SECONDARY
Time From Last Dosing to the Maximum Measured Concentration of Empagliflozin in Plasma (Tmax)
2.33; 2.17
SECONDARY
Time From Last Dosing to the Maximum Measured Concentration of Metformin in Plasma (Tmax)
4.00; 4.00
SECONDARY
Percentage (%) of the AUC of Empagliflozin That Has Been Derived After Extrapolation
9.77; 9.31
SECONDARY
Percentage (%) of the AUC of Metformin That Has Been Derived After Extrapolation
14.35; 13.04
SECONDARY
Terminal Half-life of Empagliflozin in Plasma (t1/2)
0.08; 0.08
SECONDARY
Terminal Half-life of Metformin in Plasma (t1/2)
0.06; 0.06
SECONDARY
Elimination Rate Constant (Kel) for Empagliflozin
0.93; 0.84
SECONDARY
Elimination Rate Constant (Kel) for Metformin
1.33; 0.97

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05083949). 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. Informational only — not medical advice.

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