Dose Proportionality of Different Dose Strengths of Linagliptin Tablets After Oral Administration to Healthy Male and Female Volunteers

Assessment of Dose Proportionality of Different Dose Strengths of Linagliptin Tablets After Oral Administration to Healthy Male and Female Volunteers in an Open, Randomised, Multiple-dose, Three-period Crossover, Phase I Trial

Study to assess the pharmacokinetics and dose proportionality of 1 mg, 2.5 mg and 5 mg tablets of linagliptin

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Linagliptin, low dose; Drug: Linagliptin, medium dose; Drug: Linagliptin, high dose

• Study Type: Interventional
• Enrollment (Actual): 12
• 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 volunteers 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 ECG (electrocardiogram), clinical laboratory tests
• Age 18 to 55 years (inclusive)
• BMI (Body Mass Index) 18.5 to 29.9 kg/m2 (inclusive)
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance. Repeated measurement of a systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg
• 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/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 except if a relevant interaction can be ruled out
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
• 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 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 only:

• 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: implants, injectables, combined oral contraceptives, 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 will be asked 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: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linagliptin, low dose	Drug: Linagliptin, low dose
Experimental: Linagliptin, medium dose	Drug: Linagliptin, medium dose
Active Comparator: Linagliptin, high dose	Drug: Linagliptin, high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of linagliptin	up to 168 hours after first drug administration at each visit
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of linagliptin	up to 168 hours after first drug administration at each visit
Cτ,ss (average measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of linagliptin	up to 168 hours after first drug administration at each visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 53 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 1750	up to 168 hours after first drug administration at each visit
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of CD 1750	up to 168 hours after first drug administration at each visit
Assessment of tolerability by investigator on a 4-point scale	within 10 days after last study drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: July 4, 2014
• First Submitted That Met QC Criteria: July 4, 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 4, 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; Linagliptin
• Other Study ID Numbers: 1218.33