The Bioavailability of Rifampicin in (FDCs) Widely Used in South Africa to Treat Drug-susceptible (TB) (BIO3FDC)

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

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

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: Rimactane; Drug: Rifafour e-275; Drug: Rimactazid 150/75

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7725
      • Clinical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: sequence 1; 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; 150 mg capsules, Sandoz MCC registration # A/20.2.3/784; Other Names: Rifampicin; Drug: Rifafour e-275; 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.; Drug: Rimactazid 150/75; 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.; Other Names: Rifampicin / Isoniazid
Other: sequence 2; 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; 150 mg capsules, Sandoz MCC registration # A/20.2.3/784; Other Names: Rifampicin; Drug: Rifafour e-275; 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.; Drug: Rimactazid 150/75; 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.; Other Names: Rifampicin / Isoniazid
Other: sequence 3; 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; 150 mg capsules, Sandoz MCC registration # A/20.2.3/784; Other Names: Rifampicin; Drug: Rifafour e-275; 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.; Drug: Rimactazid 150/75; 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.; Other Names: Rifampicin / Isoniazid
Other: sequence 4; 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; 150 mg capsules, Sandoz MCC registration # A/20.2.3/784; Other Names: Rifampicin; Drug: Rifafour e-275; 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.; Drug: Rimactazid 150/75; 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.; Other Names: Rifampicin / Isoniazid
Other: sequence 5; 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; 150 mg capsules, Sandoz MCC registration # A/20.2.3/784; Other Names: Rifampicin; Drug: Rifafour e-275; 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.; Drug: Rimactazid 150/75; 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.; Other Names: Rifampicin / Isoniazid
Other: sequence 6; 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; 150 mg capsules, Sandoz MCC registration # A/20.2.3/784; Other Names: Rifampicin; Drug: Rifafour e-275; 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.; Drug: Rimactazid 150/75; 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.; Other Names: Rifampicin / Isoniazid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax	1 year

Other Outcome Measures

Outcome Measure	Time Frame
AUC to 12 h	1 year
AUC to infinity	1 year

Collaborators and Investigators

• Sponsor: University of Cape Town
• Investigators: Principal Investigator: Helen M McIlleron, PhD, University of Cape Town

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: September 5, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: May 9, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Rifampin; Isoniazid
• Other Study ID Numbers: BIO3FDC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes