Pharmacokinetics of Simvastatin and Its Metabolite Simvastatin Acid With and Without Concomitant Administration of Telmisartan in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Telmisartan; Drug: Simvastatin; Drug: Telmisartan placebo

• Registration Number: NCT02187536
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

To assess the pharmacokinetics of simvastatin and simvastatin acid with/without concomitant administration of telmisartan

Detailed Description

Not available

Study Timeline

• Study Start: 2000-04
• Primary Completion: 2000-05
• Status Verified: 2014-07
• Study First Submitted: 2014-07-09
• Study First Submitted QC: 2014-07-09
• Last Update Submitted: 2014-07-09
• Study First Posted: 2014-07-11
• Last Update Posted: 2014-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Healthy subjects as determined by results of screening
• Signed written informed consent in accordance with good clinical practice (GCP) and local legislation
• Age ≥ 18 and ≤ 55 years
• Broca ≥ -20 % and ≤ +20 %

Exclusion Criteria

• Any findings of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastro-intestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Supine blood pressure at screening of systolic ≤ 110 mmHg and diastolic ≤ 60 mmHg
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infection
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of drugs with a long half life (> 24 hours) ≤ 1 month prior to administration or during the trial
• Use of any drugs which might influence the results of the trial (≤ 10 days prior to administration or during the trial)
• Participation in another trial with an investigational drug (30 days prior to administration or during the trial)
• Smoker
• Alcohol abuse (> 60 g/day)
• Drug abuse
• Blood donation (≤ 1 month prior to administration or during the trial)
• Excessive physical activities (≤ 5 days prior to administration or during the trial)
• Any laboratory value outside the reference range of clinical relevance
• Hypersensitivity to telmisartan and/or simvastatin and/or related classes of drugs

For female subjects:

• Pregnancy
• Positive pregnancy test
• No adequate contraception (e.g. sterilization, intrauterine device (IUD), oral contraceptives)
• Inability to maintain this adequate contraception during the whole study period
• Lactation period

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Telmisartan combined with Simvastatin	Simvastatin	Telmisartan once daily (day 1 to day 6) and Simvastatin given once (day 6)
Telmisartan combined with Simvastatin	Telmisartan	Telmisartan once daily (day 1 to day 6) and Simvastatin given once (day 6)
Simvastatin and telmisartan placebo	Telmisartan placebo	Telmisartan placebo once daily (day 1 to day 6) and Simvastatin given once (day 6)
Simvastatin and telmisartan placebo	Simvastatin	Telmisartan placebo once daily (day 1 to day 6) and Simvastatin given once (day 6)

Primary Outcome Measures

Name	Time	Method
Area under the concentration-time curve of simvastatin and simvastatin acid in plasma at different time points (AUC)	Pre-dose, up to day 32 after start of treatment
Maximum concentration of simvastatin and simvastatin acid in plasma (Cmax)	Pre-dose, up to day 32 after start of treatment

Secondary Outcome Measures

Name	Time	Method
Time to Cmax after a single extravascular dose (tmax)	Pre-dose, up to day 32 after start of treatment
Apparent volume of distribution during the terminal phase (Vz/f)	Pre-dose, up to day 32 after start of treatment
Maximum concentration of telmisartan in plasma at steady state (Cmax,ss)	Pre-dose, up to day 32 after start of treatment
Number of patients with clinically relevant findings in laboratory values	Pre-dose, up to day 32 after start of treatment
Area under the plasma concentration-time curve of telmisartan at steady state (AUCss)	Pre-dose, up to day 32 after start of treatment
Elimination half-life in plasma (t1/2)	Pre-dose, up to day 32 after start of treatment
Total clearance from plasma (CLtot/f)	Pre-dose, up to day 32 after start of treatment
Mean time of residence in the body (MRTtot)	Pre-dose, up to day 32 after start of treatment
Number of patients with clinically relevant findings in vital signs (blood pressure, pulse rate)	Pre-dose, up to day 32 after start of treatment
Number of patients with adverse events	Up to day 32 after start of treatment
Number of patients with clinically relevant findings in ECG	Pre-dose, up to day 32 after start of treatment