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

NCT02266485 | Completed Phase 1

• 1 other identifier: 525.3
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (22)

• 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

Study Arms (3)

BIBB 515 BS

EXPERIMENTAL

Drug: BIBB 515 BS

Pravastatin

ACTIVE COMPARATOR

Drug: Pravastatin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BIBB 515 BS DRUG

BIBB 515 BS

Pravastatin DRUG

Pravastatin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

Pravastatin

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2014
• First Posted: October 17, 2014
• Study Start: July 1, 1998
• Primary Completion: September 1, 1998
• Last Updated: October 17, 2014

Record last verified: 2014-10