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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00561925




Registration number
NCT00561925
Ethics application status
Date submitted
20/11/2007
Date registered
21/11/2007
Date last updated
7/04/2014

Titles & IDs
Public title
VERxVE Study on Efficacy and Safety of Nevirapine XR in Comparison to Nevirapine IR With Truvada in Naive HIV+ Patients
Scientific title
A Randomised, Double Blind, Double Dummy, Parallel Group, Active Controlled Trial to Evaluate the Antiviral Efficacy of 400 mg QD neVirapine Extended Release Formulation in Comparison to 200 mg BID neVirapinE Immediate Release in Combination With Truvada® in Antiretroviral Therapy naïve HIV-1 Infected Patients (VERxVE)
Secondary ID [1] 0 0
2007-003654-29
Secondary ID [2] 0 0
1100.1486
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - nevirapine IR
Treatment: Drugs - nevirapine XR

Experimental: nevirapine XR - 400 mg QD

Active Comparator: nevirapine IR - 200 mg BID


Treatment: Drugs: nevirapine IR
200 mg BID

Treatment: Drugs: nevirapine XR
400 mg QD

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population - Primary endpoint was the number of patients with a sustained virologic response through week 48 using LLOQ = 50 copies/mL
Timepoint [1] 0 0
week 48
Secondary outcome [1] 0 0
Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
Timepoint [1] 0 0
week 0 to 144
Secondary outcome [2] 0 0
Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population - Endpoint was the number of patients with a sustained virologic response through week 144 using LLOQ = 50 copies/mL
Timepoint [2] 0 0
week 144
Secondary outcome [3] 0 0
Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population
Timepoint [3] 0 0
week 0 to 144
Secondary outcome [4] 0 0
Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population
Timepoint [4] 0 0
baseline, week 144
Secondary outcome [5] 0 0
Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population
Timepoint [5] 0 0
baseline, week 144
Secondary outcome [6] 0 0
Occurrence of Rashes - Frequency of patients with drug related rash events by functional grouping
Timepoint [6] 0 0
until last patient completed 144 weeks (up to 193 weeks)
Secondary outcome [7] 0 0
Occurrence of Elevations in Laboratory Measurement by DAIDS Grade
Timepoint [7] 0 0
until last patient completed 144 weeks (up to 193 weeks)
Secondary outcome [8] 0 0
Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication
Timepoint [8] 0 0
week 0 to 144
Secondary outcome [9] 0 0
Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities
Timepoint [9] 0 0
week 0 to 72
Secondary outcome [10] 0 0
Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities
Timepoint [10] 0 0
week 0 to 72
Secondary outcome [11] 0 0
Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events
Timepoint [11] 0 0
week 0 to 72
Secondary outcome [12] 0 0
Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash
Timepoint [12] 0 0
week 0 to 72
Secondary outcome [13] 0 0
Relative Bioavailability Trough C_pre,ss,1 - Relative bioavailability measured of trough concentrations. Analysis based on adjusted by-treatment geometric means, the adjusted geometric mean ratio of NVP XR : NVP IR and it's 90% confidence interval with p-value and the inter-individual geometric coefficient of variation.
Timepoint [13] 0 0
week 132
Secondary outcome [14] 0 0
Occurrence of Hepatic Events - Frequency of patients with hepatitis symptoms
Timepoint [14] 0 0
until last patient completed 144 weeks (up to 193 weeks)

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Signed informed consent in accordance with Good Clinical Practice and local regulatory
requirements prior to trial participation

2. HIV-1 infected males or females >= 18 years of age with positive serology (ELISA)
confirmed by Western blot

3. No previous antiretroviral treatment

4. Males with CD4+ counts >50 - <400 cells/ml or females with CD4+ counts >50-<250
cells/ml

5. Adequate renal function defined as a calculated creatinine clearance (CLCr) greater
than or equal to 50 mL/min according to the Cockcroft-Gault formula as follows:

Male: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in
mg/dl) = CLCr (mL/min).

Female: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in
mg/dl) x 0.85 = CLCr (mL/min).

6. Karnofsky score >70 (see Appendix 10.4)

7. An HIV-1 viral load of 1,000 copies/mL

8. Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent important
opportunistic infections as defined in Appendix 10.2

9. Willingness to abstain from ingesting substances which may alter plasma study drug
levels by interaction with the cytochrome P450 system (listed in Appendix 10.3) during
the study.

10. For centers participating in the PK substudy only: Written informed consent in
accordance with GCP and local legislation for participation in the PK substudy.
Refusal to participate in the PK substudy is not an exclusion criterion for
participation in the trial. Only study centers with previous experience and equipped
in handling PK samples are eligible for participation in the substudy.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Active drug abuse or chronic alcoholism at the investigator's discretion

2. Active hepatitis B or C disease, defined as HBsAg-positive and HBV-DNA-positive or
HCV-RNA-positive

3. Female patients of child-bearing potential who: are pregnant at screening; are breast
feeding; are planning to become pregnant; are not willing to use a barrier method of
contraception, or; are not willing to use methods of contraception other than ethinyl
estradiol containing oral contraceptives Note: During participation in this study,
females and males have to use barrier methods of contraception in addition or instead
of ethinyl estradiol containing oral contraceptives.

4. Laboratory parameters >DAIDS Grade 2

5. ALT/AST > DAIDS Grade 1

6. Hypersensitivity to any ingredients of the test products

7. Previous use of Viramune® (nevirapine) or any other antiretroviral agents (does not
include use of single dose NVP for the prevention of mother to child transmission)

8. Resistance to NNRTIs or either one of the components of Truvada® (emtricitabine or
tenofovir disoproxil fumarate) or lamivudine (3TC) based on HIV-1 genotypic resistance
testing report obtained at screening

9. Patients who are receiving other concomitant treatments which are not permitted, as
described in the prescribing information

10. Use of investigational medications (any experimental agent other than the study
regimen) within 30 days before study entry or during the trial

11. Use of immunomodulatory drugs within 30 days before study entry or during the trial
(e.g., interferon, cyclosporin, hydroxyurea, interleukin 2)

12. Patients who have been diagnosed with malignant disease

13. Patients who in the opinion of the investigator are not candidates for inclusion in
the study

14. Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's
Sarcoma (KS), and/or any lymphoma

15. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment
for at least 12 weeks at screening visit

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
1100.1486.6101 Boehringer Ingelheim Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
1100.1486.6102 Boehringer Ingelheim Investigational Site - Darlinghurst
Recruitment hospital [3] 0 0
1100.1486.6104 Boehringer Ingelheim Investigational Site - Surry Hills
Recruitment hospital [4] 0 0
1100.1486.6103 Boehringer Ingelheim Investigational Site - Brisbane
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- Surry Hills
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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California
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District of Columbia
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Florida
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Georgia
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Idaho
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Illinois
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Kentucky
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Michigan
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North Carolina
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Ohio
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Texas
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Virginia
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Argentina
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Capital Federal
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Argentina
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Mar del Plata
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Quilmes
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Rosario
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Brugge
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Brussel
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Bruxelles
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Charleroi
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Gent
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Liège
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Botswana
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Francistown
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Gaborone
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Ontario
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Edenvale
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Nelspruit
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Port Elizabeth
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South Africa
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Pretoria
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Spain
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Alcalá de Henares (Madrid)
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Spain
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Barcelona
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Spain
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L'Hospitalet de Llobregat
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Madrid
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Mataro
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Valencia
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Switzerland
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Basel
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Bern
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Genève
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Lausanne
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Lugano
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St. Gallen
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Zürich
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Birmingham
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London
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Manchester
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United Kingdom
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Plaistow, London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the efficacy of 400 mg QD nevirapine
extended release (NVP XR) formulation versus 200 mg BID nevirapine immediate release (NVP IR)
in ARV therapy naïve HIV-1 infected patients after 48 weeks of treatment. Secondary
objectives are to evaluate safety and pharmacokinetics of NVP XR and NVP IR.
Trial website
https://clinicaltrials.gov/show/NCT00561925
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications