Clinical trial NCT02229773: Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability of BIBB 1464 (Tablet) in Hyperlipemic Healthy Male Subjects
Official title: Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability After Multiple Oral Doses of 0.25 mg, 0.5 mg and 1 mg o.d. BIBB 1464 (Tablet) or Pravastatin 20 mg Over 2 Weeks in Hyperlipemic Healthy Male Subjects (Parallel Group Comparison, Randomized, Placebo Controlled, Partly Double Blind [Pravastatin Open])
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-09-01
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Percentage change of LDL plasma cholesterol
timeFrame: baseline, 2 weeks
measure: Percentage change of total plasma cholesterol
timeFrame: baseline, 2 weeks
Secondary outcomes:
measure: Percentage change in lipid profile
timeFrame: baseline, 1 week
measure: Number of patients with adverse events
timeFrame: Up to day 42
measure: Number of patients with clinical significant findings in eye lens opacification
timeFrame: Up to day 42
measure: Number of patients with clinical significant findings in laboratory parameters
timeFrame: Up to day 28
measure: Number of patients with clinical significant findings in electrocardiogram (ECG)
timeFrame: Up to day 28
measure: Number of patients with clinical significant findings in physical examination
timeFrame: Up to day 28
measure: Number of patients with clinical significant findings in vital signs
timeFrame: Up to day 15
measure: Investigator assessed tolerability on a 4 point scale
timeFrame: day 42
measure: Amount of drug excreted in urine
timeFrame: Up to day 15
measure: Drug plasma concentration
timeFrame: Up to day 28
measure: Monoepoxysqualene (MES) plasma concentration
timeFrame: Up to day 28
Other outcomes:
Locations:
Study officials:
References: