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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02194179
First received: July 17, 2014
Last updated: NA
Last verified: July 2014
History: No changes posted
  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: 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cmax,ss / Cmin,ss ratio [ Time Frame: up to day 22 ] [ Designated as safety issue: No ]
  • %PTF (percentage peak-trough fluctuation) [ Time Frame: up to day 22 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) [ Time Frame: up to day 22 ] [ Designated as safety issue: No ]
  • Cavg (average measured concentration of the analyte in plasma at steady state) [ Time Frame: up to day 22 ] [ Designated as safety issue: No ]
  • Number of patients with adverse events (AEs) [ Time Frame: up to day 57 ] [ Designated as safety issue: No ]
  • Number of patients with clinically relevant changes in clinical laboratory tests [ Time Frame: Baseline, up to day 37 ] [ Designated as safety issue: No ]
  • Number of patients with abnormal detectable viral load [ Time Frame: Baseline, up to day 37 ] [ Designated as safety issue: No ]
  • Number of patients with clinically relevant changes in vital signs (blood pressure, pulse rate) [ Time Frame: Baseline, up to day 37 ] [ Designated as safety issue: No ]
  • Number of patients with clinically relevant changes in 12-lead electrocardiogram (ECG) [ Time Frame: Baseline, day 23 ] [ Designated as safety issue: No ]
  • Number of patients with clinically relevant changes in physical examination [ Time Frame: Baseline, up to day 37 ] [ Designated as safety issue: No ]
  • Assessment of tolerability by the investigator on a 4-point scale [ Time Frame: up to day 37 ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02194179     History of Changes
Other Study ID Numbers: 1100.1489
Study First Received: July 17, 2014
Last Updated: July 17, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Switzerland: Swissmedic

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Nevirapine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014