Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability of BIBB 1464 (Tablet) in Hyperlipemic Healthy Male Subjects

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: BIBB 1464 MS low dose; Drug: Placebo; Drug: Pravastatin; Drug: BIBB 1464 MS high dose; Drug: BIBB 1464 MS medium dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT02229773

1178.2

Details and patient eligibility

About

Lipid lowering effect, investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, monoepoxysqualene (MES) as marker), safety / tolerability and preliminary pharmacokinetics

Enrollment: 100 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy male Caucasian subjects as determined by results of screening
• Written informed consent in accordance with GCP and local legislation given
• Age >= 18 and <= 65 years
• Broca >= - 20% and <= + 30%
• LDL-cholesterol level >= 3.3 mmol/L at pre-screening and at the two screening visits

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 (including thyroid) disorder
• Surgery of the gastro-intestinal tract (except appendectomy)
• Disease of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History or orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged 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 result of the trial (<= 10 days prior to administration or during the trial)
• Participation in another trial with an investigational drug (<= 2 month prior to administration or during the trial)
• Smoker (> 10 cigarettes or > 3 cigars or >3 pipes/day)
• Inability to refrain from smoking during the period of the study
• Alcohol abuse (>60/g/day)
• Drug abuse
• Blood donation (>400ml <=1 month prior to administration)
• Excessive physical activities (<=5 days prior to administration)
• Any laboratory value outside the normal range of clinical relevance
• LDL - cholesterol screening measurements day -1 and day -7 the different between these two values exceed 12% of the higher dose
• subjects who are vegetarian

Eye-lens

• Cataract extraction in one or both eyes deemed likely within 2 years ("senile", non-idiopathic will not automatically exclude patients from participation)
• Lens Opacities Classification System (LOCS) III grade >3.0 (for nuclear opalescence or cortical grad) >0.5 (for posterior sub capsular grad)
• Log MAR Bailey-Lovie visual acuity >0.5
• Corneal or conjunctival problems which would preclude lens photography
• Shallow anterior chamber with risk of angle-closure glaucoma
• Pupil will not dilate to at least 6 mm
• Visually significant fundus pathology in clinician's judgment
• Amblyopia, optic nerve disease, iritis, history of eye surgery, argon or YAG laser, major eye trauma, extended use (daily for >3 month) of ocular or systemic corticosteroid treatment , use of anticoagulants, or glaucoma therapy, or participation in another clinical trial investigation an anti-cataract or cataractogenic formulation within the last year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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100 participants in 5 patient groups, including a placebo group

BIBB 1464 MS low dose

Experimental group

Treatment:

Drug: BIBB 1464 MS low dose

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Pravastatin

Active Comparator group

Treatment:

Drug: Pravastatin

BIBB 1464 MS medium dose

Experimental group

Treatment:

Drug: BIBB 1464 MS medium dose

BIBB 1464 MS high dose

Experimental group

Treatment:

Drug: BIBB 1464 MS high dose