Clinical trial NCT01424670: Safety and Efficacy Trial of Delamanid for 6 Months in Participants With Multidrug-resistant Tuberculosis
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Evaluate the Safety and Efficacy of Delamanid (OPC-67683) Administered Orally as 200 mg Total Daily Dose for Six Months in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multidrug-resistant Tuberculosis
Keywords: Multidrug-resistant tuberculosis
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-29
Enrollment: 511
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Time To Sputum Culture Conversion (SCC) During 6-Month Intensive Period Using The Mycobacteria Growth Indicator Tube (MGIT) System
timeFrame: Month 6
Secondary outcomes:
measure: Proportion of Participants With SCC At 2 And 6 Months Using MGIT
timeFrame: Month 2 and Month 6
measure: Proportion of Participants With Sustained SCC At Month 18, Month 24, And Month 30 Using MGIT
timeFrame: Month 18, Month 24, and Month 30
measure: Treatment Outcomes Assessed By Principal Investigators (PI)At The End Of Treatment With OBR
timeFrame: Month 24
measure: Number of Participants Who Developed Resistance To Delamanid
timeFrame: Up to Month 30
measure: Mean (Time Averaged) Area Under The Curve (AUC) Of Change From Baseline In Time To Detection (TTD) To Month 6 Using MGIT
timeFrame: Baseline, up to Month 6
measure: Mean Change From Baseline In TTD Using The MGIT System
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 24, Week 26, and Last visit (Month 18 or last visit for participants treated beyond Month 18)
measure: Proportion of Participants With Final Outcome At Month 30 As A Treatment Success Or Failure (Including Relapse) Using MGIT
timeFrame: Month 30
Other outcomes:
Locations:
city: Tartu
country: Estonia
city: Riga
country: Latvia
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Chisinau
country: Moldova, Republic of
city: Vorniceni
country: Moldova, Republic of
city: Alfonso Ugarte
country: Peru
city: Comas
country: Peru
city: El Agustino
country: Peru
city: Lima Cercado
country: Peru
city: Dasmariñas
country: Philippines
state: Cavite
city: Quezon City
country: Philippines
state: Metro Manila
city: Makati City
country: Philippines
city: Quezon City
country: Philippines
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Klerksdorp
country: South Africa
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Global Clinical Development
role: STUDY_DIRECTOR
References:
citation: 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.