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

Pharmacokinetics of Single Oral Doses of 40 mg Simvastatin and Its Metabolite Simvastatin Acid With and Without Concomitant Administration of Telmisartan 80 mg Daily, Given Orally Over 6 Days. A Randomised, Placebo Controlled, Double Blind (for Telmisartan), Two Way Cross Over Trial in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Telmisartan; Drug: Simvastatin; Drug: Telmisartan placebo

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telmisartan combined with Simvastatin; Telmisartan once daily (day 1 to day 6) and Simvastatin given once (day 6)	Drug: Telmisartan; Drug: Simvastatin
Active Comparator: Simvastatin and telmisartan placebo; Telmisartan placebo once daily (day 1 to day 6) and Simvastatin given once (day 6)	Drug: Simvastatin; Drug: Telmisartan placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Time to Cmax after a single extravascular dose (tmax)	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
Apparent volume of distribution during the terminal phase (Vz/f)	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
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
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2000
• Primary Completion (Actual): May 1, 2000

Study Registration Dates

• First Submitted: July 9, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Estimate): July 11, 2014
• Last Update Submitted That Met QC Criteria: July 9, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Simvastatin; Telmisartan
• Other Study ID Numbers: 502.341