The Bioavailability of Rifampicin in (FDCs) Widely Used in South Africa to Treat Drug-susceptible (TB)

Study Overview
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Brief Summary
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3-way cross-over single dose design evaluating bioavailability of 2 rifampicin-containing FDCs vs a single drug comparator in healthy volunteers

Detailed Description
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In this study the 4- and 2-drug FDCs (for intensive and continuation phases respectively) widely used within the South African treatment program will be evaluated in a comparative bioavailability study against a single drug rifampicin product registered by the South African Medicines Control Council. A three-way, single dose, cross-over study will be conducted in 24 healthy volunteers

Official Title
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The Bioavailability of Rifampicin in Fixed Dose Combinations (FDCs) Widely Used in South Africa to Treat Drug-susceptible Tuberculosis (TB)

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Rimactane
* Drug: Rifafour e-275
* Drug: Rimactazid 150/75


Participation Criteria
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Eligibility Criteria
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Inclusion You need to be between the ages of 18-55 years Have a Body mass index (BMI) of 19-30 kg/m2 Weigh 45 kg or more Be a non-smoker Be found to be in normal health on history and examination To have normal blood and urine test results If you are a woman of child-bearing age, you need to be prepared to not have sexual intercourse, or use a safe form of contraception, until the end of the study Exclusion You are unable to fully understand and comply with the study procedures, requirements and time commitments. Are currently enrolled in any other study evaluating drugs, biologics or devices You have TB, or have had TB before You abuse or have abused drugs or alcohol You have, or have had, drug allergy, severe asthma, or active or recurrent allergic disease You are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: sequence 1<br>Rifafour e-275®, Sanofi-Aventis /Rimactazid 150/75, Sandoz/ Rimactane® 150 mg capsules, Sandoz - 24 healthy volunteers will receive single doses of the 3 rifampicin containing products with a washout of 14 days between doses. Each volunteer will be randomised to receive the 3 doses in one of 6 sequences | Drug: Rimactane<br>* 150 mg capsules, Sandoz MCC registration # A/20.2.3/784<br>* Other names: Rifampicin;Drug: Rifafour e-275<br>* Rifampicin/isoniazid/pyrazinamide/ethambutol 150/75/400/275 mg This 4-drug FDC is the most widely used 4-drug FDC in South Africa with an estimated 100% of the SA DOH tender.<br>Drug: Rimactazid 150/75<br>* Rifampicin/isoniazid 150/75 mg This 2-drug FDC is one of 2 widely used 2-drug FDCs in South Africa, with an estimated 30% of the SA DOH tender. Rifinah® made by Sanofi-Aventis holds about 70% of the tender, however as the Sanofi-Aventis 4-drug FDC will also be evaluated.<br>* Other names: Rifampicin / Isoniazid;|
| Other: sequence 2<br>Rifafour e-275®, Sanofi-Aventis /Rimactazid 150/75, Sandoz/ Rimactane® 150 mg capsules, Sandoz - 24 healthy volunteers will receive single doses of the 3 rifampicin containing products with a washout of 14 days between doses. Each volunteer will be randomised to receive the 3 doses in one of 6 sequences | Drug: Rimactane<br>* 150 mg capsules, Sandoz MCC registration # A/20.2.3/784<br>* Other names: Rifampicin;Drug: Rifafour e-275<br>* Rifampicin/isoniazid/pyrazinamide/ethambutol 150/75/400/275 mg This 4-drug FDC is the most widely used 4-drug FDC in South Africa with an estimated 100% of the SA DOH tender.<br>Drug: Rimactazid 150/75<br>* Rifampicin/isoniazid 150/75 mg This 2-drug FDC is one of 2 widely used 2-drug FDCs in South Africa, with an estimated 30% of the SA DOH tender. Rifinah® made by Sanofi-Aventis holds about 70% of the tender, however as the Sanofi-Aventis 4-drug FDC will also be evaluated.<br>* Other names: Rifampicin / Isoniazid;|
| Other: sequence 3<br>Rifafour e-275®, Sanofi-Aventis /Rimactazid 150/75, Sandoz/ Rimactane® 150 mg capsules, Sandoz - 24 healthy volunteers will receive single doses of the 3 rifampicin containing products with a washout of 14 days between doses. Each volunteer will be randomised to receive the 3 doses in one of 6 sequences | Drug: Rimactane<br>* 150 mg capsules, Sandoz MCC registration # A/20.2.3/784<br>* Other names: Rifampicin;Drug: Rifafour e-275<br>* Rifampicin/isoniazid/pyrazinamide/ethambutol 150/75/400/275 mg This 4-drug FDC is the most widely used 4-drug FDC in South Africa with an estimated 100% of the SA DOH tender.<br>Drug: Rimactazid 150/75<br>* Rifampicin/isoniazid 150/75 mg This 2-drug FDC is one of 2 widely used 2-drug FDCs in South Africa, with an estimated 30% of the SA DOH tender. Rifinah® made by Sanofi-Aventis holds about 70% of the tender, however as the Sanofi-Aventis 4-drug FDC will also be evaluated.<br>* Other names: Rifampicin / Isoniazid;|
| Other: sequence 4<br>Rifafour e-275®, Sanofi-Aventis /Rimactazid 150/75, Sandoz/ Rimactane® 150 mg capsules, Sandoz - 24 healthy volunteers will receive single doses of the 3 rifampicin containing products with a washout of 14 days between doses. Each volunteer will be randomised to receive the 3 doses in one of 6 sequences | Drug: Rimactane<br>* 150 mg capsules, Sandoz MCC registration # A/20.2.3/784<br>* Other names: Rifampicin;Drug: Rifafour e-275<br>* Rifampicin/isoniazid/pyrazinamide/ethambutol 150/75/400/275 mg This 4-drug FDC is the most widely used 4-drug FDC in South Africa with an estimated 100% of the SA DOH tender.<br>Drug: Rimactazid 150/75<br>* Rifampicin/isoniazid 150/75 mg This 2-drug FDC is one of 2 widely used 2-drug FDCs in South Africa, with an estimated 30% of the SA DOH tender. Rifinah® made by Sanofi-Aventis holds about 70% of the tender, however as the Sanofi-Aventis 4-drug FDC will also be evaluated.<br>* Other names: Rifampicin / Isoniazid;|
| Other: sequence 5<br>Rifafour e-275®, Sanofi-Aventis /Rimactazid 150/75, Sandoz/ Rimactane® 150 mg capsules, Sandoz - 24 healthy volunteers will receive single doses of the 3 rifampicin containing products with a washout of 14 days between doses. Each volunteer will be randomised to receive the 3 doses in one of 6 sequences | Drug: Rimactane<br>* 150 mg capsules, Sandoz MCC registration # A/20.2.3/784<br>* Other names: Rifampicin;Drug: Rifafour e-275<br>* Rifampicin/isoniazid/pyrazinamide/ethambutol 150/75/400/275 mg This 4-drug FDC is the most widely used 4-drug FDC in South Africa with an estimated 100% of the SA DOH tender.<br>Drug: Rimactazid 150/75<br>* Rifampicin/isoniazid 150/75 mg This 2-drug FDC is one of 2 widely used 2-drug FDCs in South Africa, with an estimated 30% of the SA DOH tender. Rifinah® made by Sanofi-Aventis holds about 70% of the tender, however as the Sanofi-Aventis 4-drug FDC will also be evaluated.<br>* Other names: Rifampicin / Isoniazid;|
| Other: sequence 6<br>Rifafour e-275®, Sanofi-Aventis /Rimactazid 150/75, Sandoz/ Rimactane® 150 mg capsules, Sandoz - 24 healthy volunteers will receive single doses of the 3 rifampicin containing products with a washout of 14 days between doses. Each volunteer will be randomised to receive the 3 doses in one of 6 sequences | Drug: Rimactane<br>* 150 mg capsules, Sandoz MCC registration # A/20.2.3/784<br>* Other names: Rifampicin;Drug: Rifafour e-275<br>* Rifampicin/isoniazid/pyrazinamide/ethambutol 150/75/400/275 mg This 4-drug FDC is the most widely used 4-drug FDC in South Africa with an estimated 100% of the SA DOH tender.<br>Drug: Rimactazid 150/75<br>* Rifampicin/isoniazid 150/75 mg This 2-drug FDC is one of 2 widely used 2-drug FDCs in South Africa, with an estimated 30% of the SA DOH tender. Rifinah® made by Sanofi-Aventis holds about 70% of the tender, however as the Sanofi-Aventis 4-drug FDC will also be evaluated.<br>* Other names: Rifampicin / Isoniazid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax |  | 1 year |