Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability of BIBB 515 BS or Pravastatin in Hyperlipemic Healthy Male Subjects

Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability After Multiple Oral Doses of 2.5 mg o.d. BIBB 515 BS (Capsule) or Pravastatin 20 mg Over 2 Weeks in Hyperlipemic Healthy Male Subjects (Parallel Group Comparison, Randomized, Placebo Controlled, Partly Double Blind [Pravastatin Open])

Investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, MES as marker), effect on routine lipid profile parameters, safety and preliminary pharmacokinetics

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Pravastatin; Drug: BIBB 515 BS

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male caucasian subjects as determined by results of screening
• Written informed consent in accordance with good clinical practice (GCP) and local legislation given
• Age ≥ 18 and ≤ 65 years
• Broca ≥ - 20 % and ≤ + 30 %
• Cholesterol level ≥ 5.4 mmol/l

Exclusion Criteria:

• Any finding 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 gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurologic disorders
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which was 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 (≤ 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 study days
• Alcohol abuse (> 60 g/day)
• Drug abuse
• Blood donation > 100 ml (≤ 4 weeks prior to administration or during the trial)
• Excessive physical activities (≤ 10 days prior to administration or during the trial)
• Any laboratory value outside the reference range of clinical relevance
• Abnormal findings at eye lens examination

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Active Comparator: Pravastatin	Drug: Pravastatin
Experimental: BIBB 515 BS	Drug: BIBB 515 BS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage changes in total-cholesterol		Pre-dose, up to day 15
Percentage changes in low density lipoprotein (LDL) - cholesterol		Pre-dose, up to day 15
Percentage changes in high density lipoprotein (HDL) - cholesterol		Pre-dose, up to day 15
Percentage changes in apo-lipoprotein B		Pre-dose, up to day 15
Percentage changes in lipoprotein (a)		Pre-dose, up to day 15
Percentage changes in triglycerides		Pre-dose, up to day 15
Maximum concentration of the analyte in plasma at different time points (Cmax)		Up 336 hours after first drug administration
Time to reach maximum concentration of the analyte in plasma at different time points (tmax)		Up 336 hours after first drug administration
Apparent terminal elimination half-life of the analyte in plasma (t1/2)		Up 336 hours after first drug administration
Area under the concentration-time curve of the analyte in plasma at different time points (AUC)		Up 336 hours after first drug administration
Total mean residence time of the analyte in the body (MRTtot)		Up 336 hours after first drug administration
Apparent clearance of the analyte in plasma after extravascular multiple dose administration (CL/f)		Up 336 hours after first drug administration
Apparent volume of distribution of the analyte during the terminal phase (Vz/f)		Up 336 hours after first drug administration
Terminal rate constant of the analyte in plasma (λz)		Up 336 hours after first drug administration
Number of participants with clinically relevant changes from baseline in physical examination		Pre-dose and day 15
Number of participants with clinically relevant changes from baseline in 12-lead ECG		Pre-dose and day 15
Number of participants with clinically relevant changes from baseline in lens examination		Pre-dose and day 15
Number of participants with clinically relevant changes in vital signs (blood pressure, pulse rate, body weight)		Pre-dose, up to 324 hours after first drug administration
Number of participants with clinically relevant changes in laboratory parameters		Pre-dose, up to 324 hours after first drug administration
Number of participants with adverse events		Up to 1 day after last drug administration
Global clinical assessment by the investigator		On day 15 after first drug administration
Monoepoxy-squalene (MES) plasma concentration at different time points	as surrogate marker for squalene inhibition	Pre-dose, up to day 15

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 1998
• Primary Completion (Actual): September 1, 1998

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Estimate): October 17, 2014
• Last Update Submitted That Met QC Criteria: October 16, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin
• Other Study ID Numbers: 525.3