Pharmacokinetic Study of Two Generic Co-formulations of Lopinavir/Ritonavir for HIV Infected Children (SURF)

NCT ID: NCT00665951

Last Updated: 2020-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2009-02-28

Brief Summary

This pilot pharmacokinetic study is designed to exclude a large difference (>40%) in pharmacokinetics (esp. AUC) between two new Lopimune formulations and the branded formulation. The formal bioequivalence study with adequate power will be conducted by the manufacturer. In order to get data independently from the manufacturer and to have this information in an earlier phase, this small pilot study is initiated.

The initial study showed a declined bioavailability of the granules under fasting conditions. The study has been extended with an arm determining the pharmacokinetics of the granules after food (compared to the oral solution taken with food).

Detailed Description

Cipla has developed two co-formulated forms of lopinavir/ritonavir for second-line antiretroviral therapy for children: Lopimune granules and Lopimune tablets. They contain 100mg lopinavir and 25mg ritonavir.

Primary objective of this study:

To determine the pharmacokinetic profile of lopinavir and ritonavir in two different co-formulations (Lopimune granules and Lopimune tablets) after single-dose in HIV-negative, healthy adult subjects, and to compare this to the branded product.

Secondary objective:

To evaluate the safety of single-dose administration of the two generic co-formulations of lopinavir/ritonavir and compare this to the branded product.

Conditions

HIV Infections

Keywords

pediatric; pharmacokinetics; HIV infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Kaletra tablets

Group Type: ACTIVE_COMPARATOR

Lopinavir/ritonavir

Intervention Type: DRUG

Lopinavir/ritonavir 200/50mg; 2 tablets; single dose

B

Lopimune granules

Group Type: EXPERIMENTAL

Lopinavir/ritonavir

Intervention Type: DRUG

Lopinavir/ritonavir 100/25mg; 4 sachets with granules; single dose

C

Lopimune tablets

Group Type: EXPERIMENTAL

Lopinavir/ritonavir

Intervention Type: DRUG

Lopinavir/ritonavir 100/25mg; 4 tablets; single dose

Interventions

Lopinavir/ritonavir

Lopinavir/ritonavir 200/50mg; 2 tablets; single dose

Intervention Type: DRUG

Lopinavir/ritonavir

Lopinavir/ritonavir 100/25mg; 4 sachets with granules; single dose

Intervention Type: DRUG

Lopinavir/ritonavir

Lopinavir/ritonavir 100/25mg; 4 tablets; single dose

Intervention Type: DRUG

Other Intervention Names

Kaletra; Lopimune granules; Lopimune tablets

Eligibility Criteria

Inclusion Criteria

• Subject is at least 18 and not older than 55 years of age on the day of the first dosing.
• Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing.
• Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Subject is in good age appropriate health condition
• Subject has a normal blood pressure and pulse rate, according to the investigator's judgment.
• Female subject is either not of childbearing potential, or is of childbearing potential and practicing one of the following methods of birth control: condoms, sponge, foams, jellies, diaphragm or copper intrauterine device (IUD); has a vasectomized partner; or total abstinence from sexual intercourse.

Exclusion Criteria

• Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
• Positive HIV test.
• Positive hepatitis B or C test.
• Therapy with any drug, including oral contraceptives.
• Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), gastrointestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• History of or current abuse of drugs, alcohol or solvents.
• Inability to understand the nature and extent of the trial and the procedures required.
• Participation in a drug trial within 60 days prior to the first dose.
• Donation of blood within 60 days prior to the first dose.
• Febrile illness within 3 days before the first dose.
• Pregnancy or breastfeeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Radboud University Nijmegen Medical Centre

Principal Investigators

David M Burger

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

de Kanter CT, Colbers EP, Fillekes Q, Hoitsma A, Burger DM. Pharmacokinetics of two generic co-formulations of lopinavir/ritonavir for HIV-infected children: a pilot study of paediatric Lopimune versus the branded product in healthy adult volunteers. J Antimicrob Chemother. 2010 Mar;65(3):538-42. doi: 10.1093/jac/dkp472. Epub 2010 Jan 7.

Reference Type: RESULT

PMID: 20056686 (View on PubMed)

Other Identifiers

UMCN-AKF 07.04

Identifier Type: -

Identifier Source: org_study_id