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Bioavailability of 2 Different Nevirapine Extended Release Formulations Compared to Viramune® in HIV-1 Infected Subjects

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02194179
First Posted: July 18, 2014
Last Update Posted: July 18, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
  Purpose
The objective was to establish the pharmacokinetic (PK) profile at steady state of two different nevirapine (NVP) extended release (XR) formulations at 300 mg or 400 mg daily (QD) under fasted and fed conditions in comparison with the commercially available NVP immediate release (IR) tablet at 200 mg BID (400 mg/day).

Condition Intervention Phase
HIV Infections Drug: NVP XR 400 mg (KCR 25%) Drug: NVP XR 400 mg (KCR 20%) Drug: NVP XR 300 mg (KCR 25%) Drug: NVP XR 300 mg (KCR 20%) Other: high-fat breakfast Drug: NVP IR 200 mg (Viramune®) Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Steady State Bioavailability of 2 Different Nevirapine Extended Release Formulations Compared to Steady State 400 mg of Viramune® (200 mg BID), in HIV-1 Infected Subjects, an Open Label, Non Randomised, Multidose and Multistage Parallel Group Study. (ERVIR)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time dosing interval τ) [ Time Frame: up to day 22 ]
  • Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ) [ Time Frame: up to day 22 ]
  • Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over the time dosing interval τ) [ Time Frame: up to day 22 ]

Secondary Outcome Measures:
  • Cmax,ss / Cmin,ss ratio [ Time Frame: up to day 22 ]
  • %PTF (percentage peak-trough fluctuation) [ Time Frame: up to day 22 ]
  • tmax,ss (time from dosing to the maximum concentration of the analyte in plasma at steady state over the time dosing interval τ) [ Time Frame: up to day 22 ]
  • CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) [ Time Frame: up to day 22 ]
  • Cavg (average measured concentration of the analyte in plasma at steady state) [ Time Frame: up to day 22 ]
  • Number of patients with adverse events (AEs) [ Time Frame: up to day 57 ]
  • Number of patients with clinically relevant changes in clinical laboratory tests [ Time Frame: Baseline, up to day 37 ]
  • Number of patients with abnormal detectable viral load [ Time Frame: Baseline, up to day 37 ]
  • Number of patients with clinically relevant changes in vital signs (blood pressure, pulse rate) [ Time Frame: Baseline, up to day 37 ]
  • Number of patients with clinically relevant changes in 12-lead electrocardiogram (ECG) [ Time Frame: Baseline, day 23 ]
  • Number of patients with clinically relevant changes in physical examination [ Time Frame: Baseline, up to day 37 ]
  • Assessment of tolerability by the investigator on a 4-point scale [ Time Frame: up to day 37 ]

Enrollment: 92
Study Start Date: December 2006
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NVP XR 400 mg (KCR 25%) fasted Drug: NVP XR 400 mg (KCR 25%)
Experimental: NVP XR 400 mg (KCR 25%) fed Drug: NVP XR 400 mg (KCR 25%) Other: high-fat breakfast
Experimental: NVP XR 400 mg (KCR 20%) fasted Drug: NVP XR 400 mg (KCR 20%)
Experimental: NVP XR 400 mg (KCR 20%) fed Drug: NVP XR 400 mg (KCR 20%) Other: high-fat breakfast
Experimental: NVP XR 300 mg (KCR 25%) fasted Drug: NVP XR 300 mg (KCR 25%)
Experimental: NVP XR 300 mg (KCR 25%) fed Drug: NVP XR 300 mg (KCR 25%) Other: high-fat breakfast
Experimental: NVP XR 300 mg (KCR 20%) fasted Drug: NVP XR 300 mg (KCR 20%)
Experimental: NVP XR 300 mg (KCR 20%) fed Drug: NVP XR 300 mg (KCR 20%) Other: high-fat breakfast
Active Comparator: NVP IR 200 mg (Viramune®) Drug: NVP IR 200 mg (Viramune®)

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected males or females ≥ 18 and ≤ 60 years of age
  • Body mass index 18.5 to 29.9 kg/m2, inclusive
  • Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and local legislation
  • Treated with a stable Viramune® BID based regimen since at least 12 weeks prior to study entry. If however, the subject's current Viramune® treatment consists of two 200mg tablets once daily (prescribed off label), the subject is allowed to participate if he/she agrees to switch to Viramune® 200mg twice daily, 14 days before the start of Nevirapine Extended Release.
  • An HIV-1 viral load of ≤ 50 c/mL at screening
  • Acceptable screening laboratory values that indicate adequate baseline organ function with the following exceptions:

    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)

      ≤2.5 times the upper limit of normal (ULN) (DAIDS Grade 1) or

    • Gamma-glutamyl transferase (GGT) <2.5 times ULN (DAIDS Grade 1)
  • Willingness to abstain from alcoholic beverages for 24 hours prior to intensive pharmakokinetic sampling days
  • Willingness to abstain from ingesting substances which may alter drug plasma levels by interaction with the cytochrome P450 system during the study
  • Willingness to abstain from grapefruit and grapefruit juice, Seville oranges and juice, and St John's wort or milk thistle starting 14 days prior to administration of study medication until the end of the study, and
  • Karnofsky performance score ≥70

Exclusion Criteria:

  • Current treatment with any PI
  • Participation in another trial with an investigational medicine within two months prior to Day 1 of this study
  • Serum creatinine levels >1.5 times ULN at screening
  • History of acute illness within 60 days prior to Day 1, which would make the subject, in the opinion of the investigator, unsuitable for the trial
  • History or evidence of severe illness, malignancy or any other conditions which would make the subjects, in the opinion of the investigator, unsuitable for the trial
  • Any evidence of a clinically relevant concomitant disease, including gastrointestinal, hepatic, renal 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
  • Chronic or relevant acute infections other than HIV-1 (e.g. hepatitis B virus (HBV), hepatitis C virus (HCV) co infection: A chronic or acute HBV infections is defined as: HBs Ag positive. Chronic or acute HCV infection is defined as: HCV Ab positive and 1 confirmed positive viral load measurement preceding study entry)
  • Alcohol or substance abuse within 6 months prior to screening or during the study
  • Inability to comply with protocol requirements
  • Screening laboratory values <DAIDS grade 1
  • All fertile males or females, and their respective partner(s) not willing to use two forms of effective contraception. A double-barrier method must be used. A double-barrier method is defined as e.g.: 1) a condom with spermicidal jelly or with a foam suppository; 2) a diaphragm with spermicide; or 3) a male condom and a diaphragm
  • Female of child-bearing potential who:

    • Has a positive serum pregnancy test at screening,
    • Is breastfeeding,
    • Is planning to become pregnant, or
    • Is not willing to use barrier method protection or require ethinyl estradiol administration
  • Any AIDS-defining illness that is unresolved, symptomatic, or not stable on treatment for at least 12 weeks before the screening visit
  • HIV-2 infection
  Contacts and Locations
No Contacts or Locations Provided
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02194179     History of Changes
Other Study ID Numbers: 1100.1489
First Submitted: July 17, 2014
First Posted: July 18, 2014
Last Update Posted: July 18, 2014
Last Verified: July 2014

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Nevirapine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers