Study to Evaluate the Effect of Multiple Doses of Rifampicin on the Multiple-dose Pharmacokinetics of Linagliptin in Healthy Volunteers

An Open Label, Two-period, Fixed Sequence, Phase 1 Trial to Evaluate the Effect of Multiple Doses of Rifampicin on the Multiple-dose Pharmacokinetics of Linagliptin

Investigation of the bioavailability of linagliptin after concomitant multiple oral administration of 5 mg linagliptin tablets and 600 mg rifampicin (Treatment A) in comparison to multiple oral administration of 5 mg linagliptin tablets given alone (Treatment B)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Linagliptin; Drug: Rifampicin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), clinical laboratory tests
• Age 18 to 50 years (incl.)
• 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 (incl. porphyrias), 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 with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 30 g/day if male, more than 20 g/day if female)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one 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
• Thrombocytopenia or increased liver function tests (i.e. Alanine transaminase (ALT), Aspartate transaminase (AST), bilirubin, Alkaline phosphatase (AP), Gamma-glutamyl transferase (GGT)) at screening
• prior rifampicin exposure

For female subjects:

• Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 2 months after study completion
• No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: IUD (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, 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 have to use an additional barrier method (e.g. condom, diaphragm with spermicide)
• Lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Rifampicin and Linagliptin	Drug: Linagliptin; Drug: Rifampicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the steady state concentration-time curve of linagliptin in plasma (AUCτ,ss)	up to 19 days
Maximum measured steady state concentration of linagliptin in plasma (Cmax,ss)	up to 19 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 42 days
Dipeptidyl-peptidase 4 (DPP-4) inhibition	up to 19 days
AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of CD 1790	up to 19 days
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of CD 1790	up to 19 days
Ratio of urinary concentrations of 6β-hydroxycortisol to cortisol	screening, days 1 and 6 of treatment A, days 4, 6, 8 and 12 of treatment B always in the morning before drug administration
Aet1-t2,ss ( amount of analyte that is eliminated in urine from the time point t1 to time point t2 under steady state conditions) of linagliptin	up to 19 days
fet1-t2,ss ( fraction of administered drug excreted unchanged in urine at steady state over the respective time interval, where t1 and t2 define beginning and end times of the time interval) of linagliptin	up to 19 days
Assessment of global tolerability by investigator on a 4-point scale	up to 21 days after last drug administration
Number of patients with abnormal findings in physical examination	up to 21 days after last drug administration
Number of patients with abnormal changes in laboratory parameters	up to 21 days after last drug administration
Number of patients with clinically significant changes in Vital signs (Blood Pressure (BP), Pulse Rate (PR))	up to 21 days after last drug administration
Number of patients with clinically significant changes in 12-lead ECG (electrocardiogram)	up to 21 days after last drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): October 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; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Incretins; Antitubercular Agents; Dipeptidyl-Peptidase IV Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Linagliptin; Rifampin
• Other Study ID Numbers: 1218.67