Drug Levels of Tablet and Liquid Forms of Lamivudine, Nevirapine, and Stavudine in HIV Infected Thai Children

NCT ID: NCT00312091

Last Updated: 2021-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-12-31

Study Completion Date

2008-09-30

Brief Summary

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The purpose of this study is to compare the blood levels, absorption, and breakdown of lamivudine (3TC), nevirapine (NVP), and stavudine (d4T) in a fixed-dose tablet to that of the individual liquid formulations of the same anti-HIV drugs in HIV infected Thai children.

Detailed Description

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The Thai Ministry of Public Health strives to provide the HIV infected people of Thailand with affordable antiretrovirals (ARVs). A fixed-dose combination tablet of 3TC, NVP, and d4T is recommended as first-line treatment in HIV infected adults in Thailand. There has been no similar product developed for children for several reasons: pediatric dosing is based on age, weight, or body surface area; developmental changes may influence the bioavailability and pharmacokinetics (PK) of ARVs; and medication adherence may also be a problem. The purpose of this study is to gather bioavailability and PK data in children taking a fixed-dose tablet of 3TC, NVP, and d4T. This information will then be compared to the bioavailability and PK of the individual liquid formulations of these ARVs.

This study has two stages. Stage 1 will last a minimum of 4 weeks; Stage 2 will last a minimum of 8 weeks. In Stage 1, patients will be randomly assigned to one of two arms. Arm A will receive the fixed-dose tablet twice daily for 2 weeks, then switch to the individual liquid formulations twice daily for 2 weeks. Arm B will receive the individual liquid formulations twice daily for 2 weeks, then switch to the fixed-dose tablet twice daily for 2 weeks. To encourage medication adherence, study staff will make home visits and phone calls to each patient's parent or guardian the first week of each treatment regimen. Medical history, a physical exam, and urine collection will occur on Days 11 and 25. Also on Days 11 and 25, patients will be admitted to the hospital to ensure 100% medication adherence and to provide blood for PK studies.

Stage 1 patients are not eligible for Stage 2. In Stage 2, patients will be stratified by body weight, then randomly assigned to one of two arms. Arm A will receive the fixed-dose tablet twice daily for 4 weeks, then switch to the individual liquid formulations twice daily for 4 weeks. Arm B will receive the individual liquid formulations twice daily for 4 weeks, then switch to the fixed-dose tablet twice daily for 4 weeks. To encourage medication adherence, study staff will make home visits and phone calls to each patient's parent or guardian the first week of each treatment regimen. Medical history, documentation of direct observation of therapy (DOT), a physical exam, and urine collection will occur on Days 25 and 53. Also on Days 25 and 53, patients will be admitted to the hospital to ensure 100% medication adherence and to provide blood for PK studies.

Conditions

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HIV Infections

Keywords

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Pharmacokinetics Treatment Experienced

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A, Stage 1

Tablet containing d4T, 3TC, and NVP taken orally twice daily for the first 4 weeks, then liquid formulations of d4T, 3TC, and NVP taken orally twice daily for the final 4 weeks

Group Type EXPERIMENTAL

Lamivudine, nevirapine, and stavudine fixed-dose tablet

Intervention Type DRUG

7 mg d4T, 30 mg 3TC, 50 mg NVP tablet

Lamivudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Nevirapine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Stavudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

A, Stage 2

Tablet containing d4T, 3TC, and NVP taken orally twice daily for 4 weeks, then liquid formulations of d4T, 3TC, and NVP taken orally twice daily for 4 weeks

Group Type EXPERIMENTAL

Lamivudine, nevirapine, and stavudine fixed-dose tablet

Intervention Type DRUG

7 mg d4T, 30 mg 3TC, 50 mg NVP tablet

Lamivudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Nevirapine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Stavudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

B, Stage 1

Liquid formulations of d4T, 3TC, and NVP taken orally twice daily for 2 weeks, then tablet containing d4T, 3TC, and NVP taken orally twice daily for 2 weeks

Group Type EXPERIMENTAL

Lamivudine, nevirapine, and stavudine fixed-dose tablet

Intervention Type DRUG

7 mg d4T, 30 mg 3TC, 50 mg NVP tablet

Lamivudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Nevirapine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Stavudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

B, Stage 2

Liquid formulations of d4T, 3TC, and NVP taken orally twice daily for 4 weeks, then tablet containing d4T, 3TC, and NVP taken orally twice daily for 4 weeks

Group Type EXPERIMENTAL

Lamivudine, nevirapine, and stavudine fixed-dose tablet

Intervention Type DRUG

7 mg d4T, 30 mg 3TC, 50 mg NVP tablet

Lamivudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Nevirapine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Stavudine

Intervention Type DRUG

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Interventions

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Lamivudine, nevirapine, and stavudine fixed-dose tablet

7 mg d4T, 30 mg 3TC, 50 mg NVP tablet

Intervention Type DRUG

Lamivudine

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Intervention Type DRUG

Nevirapine

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Intervention Type DRUG

Stavudine

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Intervention Type DRUG

Other Intervention Names

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GPO-Vir d4T/3TC/NVP

Eligibility Criteria

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Inclusion Criteria

* HIV infected
* On a highly active antiretroviral regimen (HAART) including NVP and 2 nucleoside reverse transcriptase inhibitors and receiving a maintenance of NVP for at least 4 weeks prior to study entry and taking the current recommended oral dose every 12 hours
* Willing to swallow or chew study drugs
* Willing to be hospitalized for the 12 hour PK studies
* Willing to use acceptable forms of contraception
* Parent or guardian willing to provide informed consent


* Between 12 to 30 kg (26.5 to 66.1 lbs)


* Between 6 to 30 kg (13.2 to 66.1 lbs)

Exclusion Criteria

* Certain abnormal laboratory values
* Require certain medications
* Grade 2 or greater vomiting within 30 days prior to study entry
* Grade 2 or greater diarrhea within 30 days prior to study entry
* History of immunological failure (CD4 percentage decrease of more than 30% within a 6-month period for children 6 years or younger OR CD4 cell count decrease of more than 30% within a 6-month period for children older than 6 years)
* Current treatment for acute serious bacterial, viral, or opportunistic infection
* History of dose-limiting toxicity requiring treatment discontinuation of any of the study drugs
* Known hypersensitivity to any of the study drugs
* Current surgical or medical problem affecting gastrointestinal motility or absorption (e.g., ileus, ulcerative colitis) or liver function
* Treatment with immune modulators or myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic drugs within 30 days prior to study entry. Patients who have received therapeutic vaccines are not excluded.
* Treatment with experimental drugs within 30 days of study entry
* Acute inflammation of the liver
* Chemotherapy for active cancer
* Any clinically significant diseases other than HIV infection or clinically significant findings that, in the investigator's opinion, may interfere with the study
* Inability to provide a reliable means of contact (e.g., telephone number)
* Pregnancy
Minimum Eligible Age

6 Months

Maximum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nirun Vanprapar, MD

Role: STUDY_CHAIR

Pediatric Infectious Unit, Department of Pediatrics, Siriraj Hopstial, Mahidol University

Locations

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Queen Sirikit National Institute of Child Health, Pediatric Infectious Unit

Bangkok, Ratchathewi, Thailand

Site Status

Siriraj Hospital Mahidol University CRS

Bangkok, Ratchathewi, Thailand

Site Status

Chiang Mai University Pediatrics-Obstetrics CRS

Chiang Mai, , Thailand

Site Status

Chonburi Hosp. CRS

Chonburri, , Thailand

Site Status

Countries

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Thailand

References

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Chokephaibulkit K, Plipat N, Cressey TR, Frederix K, Phongsamart W, Capparelli E, Kolladarungkri T, Vanprapar N. Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine. AIDS. 2005 Sep 23;19(14):1495-9. doi: 10.1097/01.aids.0000183625.97170.59.

Reference Type BACKGROUND
PMID: 16135903 (View on PubMed)

Hoody DW, Fletcher CV. Pharmacology considerations for antiretroviral therapy in human immunodeficiency virus (HIV)-infected children. Semin Pediatr Infect Dis. 2003 Oct;14(4):286-94. doi: 10.1053/j.spid.2003.09.004.

Reference Type BACKGROUND
PMID: 14724793 (View on PubMed)

King JR, Kimberlin DW, Aldrovandi GM, Acosta EP. Antiretroviral pharmacokinetics in the paediatric population: a review. Clin Pharmacokinet. 2002;41(14):1115-33. doi: 10.2165/00003088-200241140-00001.

Reference Type BACKGROUND
PMID: 12405863 (View on PubMed)

Vanprapar N, Cressey TR, Chokephaibulkit K, Muresan P, Plipat N, Sirisanthana V, Prasitsuebsai W, Hongsiriwan S, Chotpitayasunondh T, Eksaengsri A, Toye M, Smith ME, McIntosh K, Capparelli E, Yogev R; IMPAACT P1056 Team. A chewable pediatric fixed-dose combination tablet of stavudine, lamivudine, and nevirapine: pharmacokinetics and safety compared with the individual liquid formulations in human immunodeficiency virus-infected children in Thailand. Pediatr Infect Dis J. 2010 Oct;29(10):940-4. doi: 10.1097/INF.0b013e3181e2189d.

Reference Type RESULT
PMID: 20453709 (View on PubMed)

Other Identifiers

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10139

Identifier Type: REGISTRY

Identifier Source: secondary_id

PACTG P1056

Identifier Type: -

Identifier Source: secondary_id

IMPAACT P1056

Identifier Type: -

Identifier Source: secondary_id

P1056

Identifier Type: -

Identifier Source: org_study_id