Relative Bioavailability of Different Oral Viramune Extended Release Formulations Compared to Viramune® Oral Suspension in Healthy Male Volunteers

Relative Bioavailability of Different Oral Viramune Extended Release Formulations Containing 300 mg or 400 mg Compared to 200 mg or 400 mg as One or Two 200 mg IR Tablets Following Administration in Healthy Male Volunteers - an Openlabel, Non-randomized, Parallel Group Study

Study to determine the relative bioavailability of different oral Viramune Extended Release (ER) formulations compared to Viramune® Immediate Release (IR) tablet

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: NVP ER 300 mg (KCR 20%) Medium Release; Drug: NVP ER 300 mg (KCR 25%) Medium Release; Drug: NVP ER 300 mg (KCR 30%) Slow Release; Drug: NVP ER 400 mg (KCR 25%) Medium Release; Drug: NVP ER 300 mg (KCR 40%) Slow Release; Drug: NVP ER 300 mg (ECR 20%) Fast Release; Drug: NVP ER 400 mg (KCR 20%) Medium Release; Drug: NVP ER 400 mg (KCR 30%) Slow Release; Drug: NVP ER 400 mg (KCR 40%) Slow Release; Drug: NVP ER 400 mg (ECR 20%) Fast Release; Drug: Nevirapine immediate release (IR) 200 mg

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males according to the following criteria based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory
• Age ≥18 and Age ≤50 years
• Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders of clinical relevance
• Surgery of the gastrointestinal tract (except appendectomy and herniotomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 60 g/day)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a corrected QT interval (QTc) >450 ms)
• A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• History of disease which affects the present situation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nevirapine (NVP) ER 300 mg (KCR 20%) Medium Release	Drug: NVP ER 300 mg (KCR 20%) Medium Release
Experimental: NVP ER 300 mg (KCR 25%) Medium Release	Drug: NVP ER 300 mg (KCR 25%) Medium Release
Experimental: NVP ER 300 mg (KCR 30%) Slow Release	Drug: NVP ER 300 mg (KCR 30%) Slow Release
Experimental: NVP ER 400 mg (KCR 25%) Medium Release	Drug: NVP ER 400 mg (KCR 25%) Medium Release
Experimental: NVP ER 300 mg (KCR 40%) Slow Release	Drug: NVP ER 300 mg (KCR 40%) Slow Release
Experimental: NVP ER 300 mg (ECR 20%) Fast Release	Drug: NVP ER 300 mg (ECR 20%) Fast Release
Experimental: NVP ER 400 mg (KCR 20%) Medium Release	Drug: NVP ER 400 mg (KCR 20%) Medium Release
Experimental: NVP ER 400 mg (KCR 30%) Slow Release	Drug: NVP ER 400 mg (KCR 30%) Slow Release
Experimental: NVP ER 400 mg (KCR 40%) Slow Release	Drug: NVP ER 400 mg (KCR 40%) Slow Release
Experimental: NVP ER 400 mg (ECR 20%) Fast Release	Drug: NVP ER 400 mg (ECR 20%) Fast Release
Active Comparator: Nevirapine IR 1 tablet	Drug: Nevirapine immediate release (IR) 200 mg
Active Comparator: Nevirapine IR 2 tablets	Drug: Nevirapine immediate release (IR) 200 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	up to 144 hours post-dose
Cmax (maximum measured concentration of the analyte in plasma)	up to 144 hours post-dose
C24 (measured concentration of the analyte in plasma at 24 hours post-dose)	24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 36 days
Cmax/C24 ratio	up to 144 hours post-dose
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)	up to 144 hours post-dose
λz (terminal rate constant in plasma)	up to 144 hours post-dose
t1/2 (terminal half-life of the analyte in plasma)	up to 144 hours post-dose
MRTpo (mean residence time of the analyte in the body after po administration) CL/F (apparent clearance of the analyte in the plasma after extravascular administration)	up to 144 hours post-dose
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)	up to 144 hours post-dose
ka (absorption rate constant)	up to 144 hours post-dose
Assessment of tolerability by investigator on a 4-point scale	within 8 days after last trial procedure
tmax (time from dosing to the maximum concentration of the analyte in plasma)	up to 144 hours post-dose

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: July 15, 2014
• First Posted (Estimate): July 16, 2014

Study Record Updates

• Last Update Posted (Estimate): July 16, 2014
• Last Update Submitted That Met QC Criteria: July 15, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine
• Other Study ID Numbers: 1100.1485