Relative Bioavailability of Two Fixed Dose Combination Tablets of Linagliptin/Pioglitazone Compared With Single Linagliptin and Pioglitazone Tablets Administered Together to Healthy Male and Female Subjects

Relative Bioavailability of Two Fixed Dose Combination Tablets of Linagliptin 5 mg/Pioglitazone 45 mg Compared With Single Linagliptin 5 mg and Pioglitazone 45 mg Tablets Administered Together to Healthy Male and Female Subjects (Open, Randomised, Single Dose, Three-period Crossover Phase I Trial)

Determination of the relative bioavailability of 2 different formulations of a 5 mg linagliptin (BI 1356)/45 mg pioglitazone fixed dose combination (FDC) tablet, formulation C5 and formulation C8, compared with the mono-components linagliptin and pioglitazone administered together

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Linagliptin/pioglitazone, FDC formulation C5; Drug: Linagliptin/pioglitazone, FDC formulation C8; Drug: Linagliptin tablet; Drug: pioglitazone tablet (Actos®)

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female subjects according to the following criteria: based upon a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Age ≥18 and ≤55 years
• Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2
• Signed and dated written informed consent prior to admission to the study, in accordance with 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), psychiatric disorders, or neurological disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (>24 h) within at least 1 month or less than 10 halflives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial or based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
• Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 30 g/day for males and 20 g/day for females)
• Drug abuse
• Blood donation (more than 100 mL within 4 weeks prior to administration or during the trial)
• Excessive physical activities (within 1 week prior to administration or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site

For female subjects:

• Pregnancy or a positive pregnancy test, planning to become pregnant during the study, or within 1 month of study completion or lactation period
• No adequate contraception during the study and until 1 month after study completion, i.e. implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence (for at least 1 month before enrolment), vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females who did not have a vasectomised partner, were not sexually abstinent, or were not surgically sterile were asked to additionally use barrier contraception methods (i.e. condom, diaphragm with spermicide)

For male subjects:

• Male subjects who did not agree to minimise the risk of female partners becoming pregnant from the first dosing day until the completion of the post study medical examination. Acceptable methods of contraception included barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive for at least 2 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1 (T1); Linagliptin/pioglitazone, FDC formulation C5	Drug: Linagliptin/pioglitazone, FDC formulation C5; film coated tablet (5 mg/45 mg)
Experimental: Treatment 2 (T2); Linagliptin/pioglitazone, FDC formulation C8	Drug: Linagliptin/pioglitazone, FDC formulation C8; film coated tablet (5 mg/45 mg)
Active Comparator: Reference (R); Linagliptin tablet and pioglitazone tablet (Actos®)	Drug: Linagliptin tablet; 5 mg; Drug: pioglitazone tablet (Actos®); 45 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-72 (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 h)	1 hour prior drug administration and up to 120 h after drug administration
Cmax (maximum measured concentration of linagliptin in plasma)	1 hour prior drug administration and up to 120 h after drug administration
AUC0-infinity (area under the concentration-time curve of pioglitazone in plasma over the time interval from 0 extrapolated to infinity)	1 hour prior drug administration and up to 72 h after drug administration
Cmax (maximum measured concentration of pioglitazone in plasma)	1 hour prior drug administration and up to 72 h after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)	1 hour prior drug administration and up to 120 h after drug administration
AUC0-infinity (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity)	1 hour prior drug administration and up to 120 h after drug administration
AUC0-72 (area under the concentration-time curve of pioglitazone in plasma over the time interval from 0 to 72 h)	1 hour prior drug administration and up to 72 after drug administration
Changes from baseline in vital signs (blood pressure (BP) and pulse rate (PR))	21 to 1 day prior start of treatment, at study visits 2 to 4 (prior to treatment administration and 24 h following treatment administration), and 7 days after last treatment administration
Occurrence of adverse events (AEs)	until 7 days after last treatment administration
Assessment of tolerability by the investigator	on day 6 of each treatment and 7 days after last treatment administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 7, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Pioglitazone; Linagliptin
• Other Study ID Numbers: 1264.1