HIV InfectionsPhase 1NCT00905489
A Phase I Multiple Dose Pharmacokinetic Study of Nevirapine Extended Release (XR) in HIV-1 Infected Children.
A Phase 1 study testing Nevirapine Immediate Release (IR) and Nevirapine Extended Release (XR) in people with HIV Infections, run by Boehringer Ingelheim at 10 sites in 4 countries.
Trial summary
The primary objective is to establish the pharmacokinetic (PK) profile at steady state of nevirapine XR in HIV infected children from >=3 to <18 years of age. This phase I trial is an open-label, multiple dose, non-randomized and cross-over study. Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Nevirapine Immediate Release (IR) and Nevirapine Extended Release (XR)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Jun 2009to Sep 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed and dated written informed consent of a parent or legal guardian prior to admission. Active assent must be given by the patient if the child and/or adolescent is capable of understanding the provided study information.
- HIV-1 infected males or females >= 3 and < 18 years old.
- BSA >= 0.58 m2 for patients using BSA to calculate nevirapine IR dose; or BW >= 12.5 kg for patients using BW to calculate nevirapine IR dose at screening visit.
- Treated with a nevirapine IR based regimen for at least 18 weeks prior to screening visit (Visit 1); no modifications in the ARV background therapy within the last 2 weeks prior to screening.
- An HIV VL of <50 copies/mL while receiving nevirapine IR at the last measure of VL documented in the medical record obtained within a period of 5 months prior to screening visit.
- An HIV VL of <50 copies/mL at screening visit.
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- A stable or not decreasing CD4+ cell count according to the investigator's opinion.
- Acceptable screening laboratory values that indicate adequate baseline organ function according to the opinion of investigator.
- ALT and AST <= 2.5 X ULN (DAIDS Grade 1).
- Serum creatinine levels <= 1.3 X ULN (DAIDS Grade 1).
- Patients able to swallow tablets.
Who cannot join
- Any AIDS-related or AIDS defining illness that is unresolved or not stable on treatment at least 8 weeks prior to screening visit.
- Diseases other than HIV infection or conditions that, in the investigator's opinion, would interfere with the study.
- Patients who have been diagnosed with malignant disease and who are receiving systemic chemotherapy or are anticipated to receive any therapy during their participation in this trial.
- Use of investigational medications or vaccines within 28 days prior to Visit 1 or during the trial.
- Use of immunomodulatory drugs within 28 days before Visit 1 or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2).
- Concomitant protease inhibitor (PI) treatment.
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- Unwillingness to abstain from ingesting substances during the study which may alter plasma drug concentrations by interaction with the cytochrome P450 system (Appendix 10.2).
- Female patients of childbearing potential who:
- have a positive serum pregnancy test at screening,
- are breast feeding,
- are planning on becoming pregnant,
- are not willing to use double-barrier methods
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
Botswana3 sites
1100.1518.2605 Boehringer Ingelheim Investigational Site
Francistown
1100.1518.2601 Boehringer Ingelheim Investigational Site
Gaborone
1100.1518.2603 Boehringer Ingelheim Investigational Site
Gaborone
Germany3 sites
1100.1518.4902 Boehringer Ingelheim Investigational Site
Berlin
1100.1518.4901 Boehringer Ingelheim Investigational Site
Frankfurt am Main
1100.1518.4903 Boehringer Ingelheim Investigational Site
München
United States2 sites
1100.1518.0002 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania
1100.1518.0001 Boehringer Ingelheim Investigational Site
Washington D.C., District of Columbia
South Africa2 sites
1100.1518.2702 Boehringer Ingelheim Investigational Site
Cape Town
1100.1518.2703 Boehringer Ingelheim Investigational Site
Parow Valley
About this study
Official title: An Open-label, Multiple Dose, Cross-over Study to Evaluate the Steady-state Pharmacokinetic Parameters of Nevirapine Extended Release Tablets in HIV-1 Infected Children, With an Optional Extension Phase
The primary objective is to establish the pharmacokinetic (PK) profile at steady state of nevirapine XR in HIV infected children from >=3 to <18 years of age. This phase I trial is an open-label, multiple dose, non-randomized and cross-over study. Patients who have completed the last visit of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program. During this OEP, nevirapine XR safety and efficacy information will be collected.
- Conditions
- HIV Infections
- Being tested
- Nevirapine Immediate Release (IR), Nevirapine Extended Release (XR)
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nevirapine Immediate Release (IR)Drug
Also called Nevirapine IR
200 mg Tablet or 50 mg / 5 ml oral suspension
Nevirapine Extended Release (XR)Drug
Also called Nevirapine XR
200 mg, 300 mg or 400 mg Tablet formulation
| Study group | Role | What they receive |
|---|---|---|
| Nevirapine IR / Nevirapine XR | Experimental | In this pharmaco-kinetic (PK) cross-over design trial, all patients initially receive nevirapine immediate release and then all patients are switched to nevirapine extended release 200 mg, 300 mg or 400 mg QD. After completing the PK phase patients had the option of continuing treatment with nevirapine XR in the Optional Extension Phase (OEP). Receives: Drug: Nevirapine Immediate Release (IR); Drug: Nevirapine Extended Release (XR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Trough Cpre,N.
Trough Nevirapine concentration immediately prior to the next scheduled dose. Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
The measure of dispersion presented is the coefficient of variation (%) rather than the geometric coefficient of variation.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Secondary outcomes (14)
AUCt,ss
Area under the concentration-time curve of the Nevirapine (NVP) in plasma at steady state over the time dosing interval τ.
All patients received nevirapine IR for 10 days prior to collection of 12-hour Area Under the Curve (AUC) data. Then, all patients were switched to nevirapine XR for 9 days prior to collection of 24-hour AUC data. The treatments of IR and XR are summarized separately using geometric means and geometric coefficients of variation.
For NVP IR AUC measured over hours: 0,1,2,3,4,8 and 12, For NVP XR AUC measured over hours: 0,1,2,3,4,8,10,12 and 24.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
Minimum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ by nevirapine XR dose group Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 21.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
Maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Ratio Cmax,ss/Cmin,ss
Ratio of (maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ)/(minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
%PTF
Percentage peak-trough Nevirapine fluctuation, % fluctuation (degree of peak to trough fluctuation) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Tmax,ss
Time from dosing to the maximum concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
The standard deviation is actually the coefficient of variation.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
CL/F,ss
Apparent clearance of the Nevirapine in the plasma after extravascular administration at steady-state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Cavg
Average measured concentration of the Nevirapine in plasma at steady state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Measured: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Efficacy: Patients Maintaining a VL < 50 Copies/mL
Patients maintaining a viral load < 50 copies/mL at Day 22.
Measured: Day 22
Efficacy: Patients Maintaining a VL < 400 Copies/mL
Patients maintaining a viral load < 400 copies/mL at Day 22
Measured: Day 22
Change From Baseline in Mean CD4+ Count (Absolute)
Change in mean CD4+ count (absolute) from baseline to Day 22 and from baseline to Week 24.
Measured: Baseline, Day 22 and week 24
Percentage Change From Baseline in Mean CD4+ Count
((Day 22 value-Baseline value)/Baseline value)*100. ((Week 24 value-Baseline value)/Baseline value)*100.
Measured: Baseline to day 22 and baseline to week 24
Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase
Patients maintaining a viral load < 50 copies/mL at week 24 (approximately 168 days) of Optional Extension Phase (OEP).
Measured: week 24
Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase
Patients maintaining a viral load < 400 copies/mL at week 24 of the Optional Extension Phase (OEP)
Measured: week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2009 (estimated)
- Study startJun 2009
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00905489
- Sponsor's protocol ID
- 1100.1518
- Other IDs
- 2008-005855-61, 2008
- Status last verified
- Dec 2015
- First submitted
- 6 May 2009
- Last updated
- 7 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multiple Dose, Cross-over Study to Evaluate the Steady-state Pharmacokinetic Parameters of Nevirapine Extended Release Tablets in HIV-1 Infected Children, With an Optional Extension Phase
- ClinicalTrials.gov ID
- NCT00905489
- Acronym / sponsor ID
- 1100.1518
- Conditions
- HIV Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 20 May 2009 (estimated)
- Results
- Posted 7 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to establish the pharmacokinetic (PK) profile at steady state of nevirapine XR in HIV infected children from >=3 to <18 years of age. This phase I trial is an open-label, multiple dose, non-randomized and cross-over study. Patients who have completed the last visit of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program. During this OEP, nevirapine XR safety and efficacy information will be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nevirapine IR / Nevirapine XR | Experimental | Drug: Nevirapine Immediate Release (IR), Drug: Nevirapine Extended Release (XR)In this pharmaco-kinetic (PK) cross-over design trial, all patients initially receive nevirapine immediate release and then all patients are switched to nevirapine extended release 200 mg, 300 mg or 400 mg QD. After completing the PK phase patients had the option of continuing treatment with nevirapine XR in the Optional Extension Phase (OEP). |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Signed and dated written informed consent of a parent or legal guardian prior to admission. Active assent must be given by the patient if the child and/or adolescent is capable of understanding the provided study information.
- HIV-1 infected males or females >= 3 and < 18 years old.
- BSA >= 0.58 m2 for patients using BSA to calculate nevirapine IR dose; or BW >= 12.5 kg for patients using BW to calculate nevirapine IR dose at screening visit.
- Treated with a nevirapine IR based regimen for at least 18 weeks prior to screening visit (Visit 1); no modifications in the ARV background therapy within the last 2 weeks prior to screening.
- An HIV VL of <50 copies/mL while receiving nevirapine IR at the last measure of VL documented in the medical record obtained within a period of 5 months prior to screening visit.
Key exclusion criteria (12 listed)
- Any AIDS-related or AIDS defining illness that is unresolved or not stable on treatment at least 8 weeks prior to screening visit.
- Diseases other than HIV infection or conditions that, in the investigator's opinion, would interfere with the study.
- Patients who have been diagnosed with malignant disease and who are receiving systemic chemotherapy or are anticipated to receive any therapy during their participation in this trial.
- Use of investigational medications or vaccines within 28 days prior to Visit 1 or during the trial.
- Use of immunomodulatory drugs within 28 days before Visit 1 or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nevirapine Immediate Release (IR)Also: Nevirapine IR200 mg Tablet or 50 mg / 5 ml oral suspension | Drug | Nevirapine IR / Nevirapine XR |
| Nevirapine Extended Release (XR)Also: Nevirapine XR200 mg, 300 mg or 400 mg Tablet formulation | Drug | Nevirapine IR / Nevirapine XR |
Primary outcome
Trough Cpre,N.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Trough Nevirapine concentration immediately prior to the next scheduled dose. Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. The measure of dispersion presented is the coefficient of variation (%) rather than the geometric coefficient of variation.
14 secondary outcomes
AUCt,ss
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Ratio Cmax,ss/Cmin,ss
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
%PTF
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Tmax,ss
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
CL/F,ss
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Cavg
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Efficacy: Patients Maintaining a VL < 50 Copies/mL
Time frame: Day 22
Efficacy: Patients Maintaining a VL < 400 Copies/mL
Time frame: Day 22
Change From Baseline in Mean CD4+ Count (Absolute)
Time frame: Baseline, Day 22 and week 24
Percentage Change From Baseline in Mean CD4+ Count
Time frame: Baseline to day 22 and baseline to week 24
Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase
Time frame: week 24
Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase
Time frame: week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nevirapine Immediate Release (IR) and Nevirapine Extended Release (XR) in people with HIV Infections, run by Boehringer Ingelheim at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Botswana, Germany, United States, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Trough Cpre,N. (time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2016.