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Phase 1 Completed N=40 Randomized Treatment

Relative Bioavailability of Two Different Batches of a Linagliptin / Metformin Combination Tablet in Healthy Volunteers

Healthy
Source: ClinicalTrials.gov NCT01216397 ↗
Enrolled (actual)
40
Serious AEs
0.0%
Results posted
Apr 2012
Primary outcomePrimary: Linagliptin: Maximum Measured Concentration (Cmax) — 5.36; 5.39 nmol/L

Summary

The objective of the current study is to investigate the relative bioavailability of two different batches of a 2.5 mg linagliptin / 1000 mg metformin fixed dose combination tablet (FDC).

Outcome Measures

OutcomeResultp-value
PRIMARY
Linagliptin: Maximum Measured Concentration (Cmax)
5.36; 5.39
PRIMARY
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
179; 179
PRIMARY
Metformin: Cmax
1790; 1820
PRIMARY
Metformin: AUC0-tz
12100; 12100
SECONDARY
Linagliptin: AUC0-infinity
267; 267
SECONDARY
Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation
32.6; 32.1
SECONDARY
Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)
3.00; 3.00
SECONDARY
Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)
0.0153; 0.0152
SECONDARY
t1/2 (Terminal Half-life of the Analyte in Plasma)
45.4; 45.6
SECONDARY
Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
64.6; 64.5
SECONDARY
Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)
330; 330
SECONDARY
Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)
1300; 1300
SECONDARY
Metformin: AUC0-infinity
12400; 12300
SECONDARY
Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation
1.51; 1.52
SECONDARY
Metformin: Tmax
1.99; 2.00
SECONDARY
Metformin: λz (Terminal Elimination Rate Constant in Plasma)
0.0493; 0.0514
SECONDARY
Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)
14.1; 13.5
SECONDARY
Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
8.27; 8.23
SECONDARY
Metformin: CL/F
1350; 1350
SECONDARY
Metformin: Vz/F
1640; 1580
SECONDARY
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
0; 0; 0; 0; 0; 0
SECONDARY
Participants With Treatment Emergent Adverse Events
6; 9; 0; 1; 2; 1
SECONDARY
Participants Who Discontinued the Trial Because of an Adverse Event
0; 0
SECONDARY
Assessment of Tolerability by the Investigator
39; 40; 1; 0

Eligibility Criteria

Inclusion criteria

  • Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
  • Age 21 to 50 years (incl.)
  • Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)
  • Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion criteria

  • Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
  • Any evidence of a clinically relevant concomitant disease
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • Surgery of the gastrointestinal tract (except appendectomy)
  • Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
  • History of relevant orthostatic hypotension, fainting spells or blackouts
  • Chronic or relevant acute infections
  • History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)
  • Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration
  • Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
  • Smoker (more than 10 cigarettes or 3 cigars 3 pipes daily)
  • Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males)
  • Drug abuse
  • Blood donation (more than 100 mL within four weeks prior to day 1 of visit 2)
  • Any laboratory value outside the reference range that is of clinical relevance
  • Inability to comply with dietary regimen of trial site

For female subjects of childbearing potential only:

  • Positive pregnancy test, pregnancy or planning to become pregnant 1 month before study or within 2 months after study completion
  • No adequate contraception 1 month before study and until 2 month after study completion, e.g. not any of the following: implants, injectables, combined hormonal contraceptives, hormonal IUD (intrauterine device), sexual abstinence for at least 1 month prior to first study drug administration, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom).
  • Lactation
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01216397). 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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