Safety and Efficacy Trial of Delamanid for 6 Months in Participants With Multidrug-resistant Tuberculosis

NCT ID: NCT01424670

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 511 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-02
• Study Completion Date: 2016-07-04

Brief Summary

The purpose of this trial is to determine whether delamanid is effective in the treatment of multidrug-resistant tuberculosis (MDR TB) in combination with other MDR TB medications during 6 months of treatment.

Detailed Description

The primary objective of this trial is to evaluate the efficacy of delamanid administered orally as 100 milligrams (mg) twice daily (BID) for 2 months followed by 200 mg once daily (QD) for 4 months in combination with an optimized background treatment regimen (OBR) versus placebo with OBR during the 6-month Intensive Period of MDR TB treatment. Following the 6-month Intensive Period, OBR was administered alone during the Continuation Period for 12 to 18 months (from Month 7 up to Month 24). The trial also included a post-treatment follow-up period of 6 to 12 months (Month 19 to Month 24 to the end of Month 30). OBR given throughout the study was administered as per World Health Organization (WHO) guidelines and national treatment norms.

This trial is a multicenter, randomized, double-blind, stratified, placebo-controlled trial that was conducted globally in 2 parallel groups at 17 sites in 7 countries qualified to treat MDR TB.

Conditions

Multidrug-resistant Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Delamanid + OBR

In the first period of this study, known as the 6-month Intensive Period, participants were randomized to receive 100 mg delamanid orally BID (morning and evening) + OBR for 2 months, followed by 200 mg delamanid QD (every morning) + OBR for 4 months.

Following the 6-month Intensive Period, participants entered the second period of the study, known as the Continuation Period, wherein OBR was administered alone for 12 to 18 months.

OBR given throughout the study was administered as per WHO guidelines and national treatment norms.

Group Type: EXPERIMENTAL

Delamanid + OBR

Intervention Type: DRUG

The assigned doses of delamanid were administered with an OBR. The selection and administration of the OBR were based on WHO's guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country.

Placebo + OBR

In the first period of this study, known as the 6-month Intensive Period, participants were randomized to receive placebo orally BID (morning and evening) + OBR for 2 months followed by placebo QD (every morning) + OBR for 4 months.

Following the 6-month Intensive Period, participants entered the second period of the study, known as the Continuation Period, wherein OBR was administered alone for 12 to 18 months.

OBR given throughout the study was administered as per WHO guidelines and national treatment norms.

Group Type: PLACEBO_COMPARATOR

Placebo + OBR

Intervention Type: DRUG

Matching placebo was administered with an OBR. The selection and administration of the OBR were based on WHO's guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country.

Interventions

Delamanid + OBR

The assigned doses of delamanid were administered with an OBR. The selection and administration of the OBR were based on WHO's guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country.

Intervention Type: DRUG

Placebo + OBR

Matching placebo was administered with an OBR. The selection and administration of the OBR were based on WHO's guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Provide written, informed consent
• Current diagnosis of MDR TB
• Chest radiograph consistent with TB
• Able to produce sputum
• Negative urine pregnancy test and agree to use a highly effective method of birth control and/or adequate method of contraception

Exclusion Criteria

• Allergy to any nitro-imidazoles or nitro-imidazole derivates
• Diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated
• Use of disallowed medications
• Renal impairment
• Abnormal electrocardiogram (ECG) results
• Cardiovascular disorders
• Body mass index (BMI) < 16 kg/m^2
• Karnofsky score < 50%
• Significant metabolic, gastrointestinal, neurological, psychiatric, or endocrine diseases, active malignancy
• Alcohol abuse
• Pregnant, breast-feeding, or planning to conceive or father a child
• Recent use of methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, tetrahydrocannabinol, barbiturates, and opiates
• Previous exposure to delamanid
• Administered an investigational medicinal product (IMP) within 1 month prior to Screening (Days -21 to -2).
• Evidence of extensively drug-resistant TB based on the definition from WHO
• Human immunodeficiency virus (HIV) co-infection for participants screened at sites not participating in the HIV subtrial (data from the HIV subtrial will be reported separately from the Clinical Study Report for Study 242-09-213).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Development

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

Tartu, , Estonia

Riga, , Latvia

Šiauliai, , Lithuania

Vilnius, , Lithuania

Chisinau, , Moldova

Vorniceni, , Moldova

Alfonso Ugarte, , Peru

Comas, , Peru

El Agustino, , Peru

Lima Cercado, , Peru

Dasmariñas, Cavite, Philippines

Quezon City, National Capital Region, Philippines

Makati City, , Philippines

Quezon City, , Philippines

Cape Town, , South Africa

Durban, , South Africa

Klerksdorp, , South Africa

Countries

Estonia; Latvia; Lithuania; Moldova; Peru; Philippines; South Africa

References

von Groote-Bidlingmaier F, Patientia R, Sanchez E, Balanag V Jr, Ticona E, Segura P, Cadena E, Yu C, Cirule A, Lizarbe V, Davidaviciene E, Domente L, Variava E, Caoili J, Danilovits M, Bielskiene V, Staples S, Hittel N, Petersen C, Wells C, Hafkin J, Geiter LJ, Gupta R. Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial. Lancet Respir Med. 2019 Mar;7(3):249-259. doi: 10.1016/S2213-2600(18)30426-0. Epub 2019 Jan 7.

Reference Type: DERIVED

PMID: 30630778 (View on PubMed)

Other Identifiers

242-09-213

Identifier Type: -

Identifier Source: org_study_id