Safety and Efficacy Trial of Delamanid for 6 Months in Patients With Multidrug Resistant Tuberculosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01424670
First received: August 25, 2011
Last updated: June 29, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Multidrug Resistant Tuberculosis
Drug: Delamanid
Drug: Placebo
Drug: Optimized Background Regimen (OBR)
Drug: Antiretrovirals (ARVs)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter,Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Evaluate the Safety and Efficacy of Delamanid Administered Orally as 200 mg Total Daily Dose for Six Months in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Time to Sputum Culture Conversion [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Distribution of the time to SCC during the 6-months of IMP treatment.


Secondary Outcome Measures:
  • Time to Sputum Culture Conversion [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Distribution of the time to SCC during the 2-months of IMP treatment

  • Mortality [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Time to mortality during the 30 month trial period

  • Treatment Success and Failure [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Proportion of patients with treatment success at the end of the 30 month trial period; success defined as achieving SCC within 26 weeks and completing the trial to the 30 month scheduled visit

  • Sputum Culture Conversion [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Proportion of patients with SCC at 2 months

  • Sputum Culture Conversion [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Proportion of patients with SCC at 6 months

  • Durability of Sputum Culture Conversion [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Durability of SCC with the MGIT system during the Continuation Treatment and Post-treatment Follow-up periods

  • Durability of Sputum Culture Conversion [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Durability of SCC with the MGIT system during the Continuation Treatment and Post-treatment Follow-up periods


Enrollment: 511
Study Start Date: September 2011
Estimated Study Completion Date: May 2017
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo tablet
Matching Placebo tablet
Drug: Placebo
Matching Placebo
Drug: Optimized Background Regimen (OBR)
• Selection and administration of the treatment medications (i.e. OBRs) will be based on WHO's Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country
Drug: Antiretrovirals (ARVs)
• HIV treatment (i.e. ARVs) will be based on WHO guidelines and recommendations, and in compliance with local/national guidelines for HIV in South Africa (each site).
Experimental: Delamanid
100mg BID for 2 months and 200mg QD for 4 months
Drug: Delamanid
100mg BID for 2 months and 200mg QD for 4 months
Drug: Optimized Background Regimen (OBR)
• Selection and administration of the treatment medications (i.e. OBRs) will be based on WHO's Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country
Drug: Antiretrovirals (ARVs)
• HIV treatment (i.e. ARVs) will be based on WHO guidelines and recommendations, and in compliance with local/national guidelines for HIV in South Africa (each site).

Detailed Description:

The purpose of this trial is to evaluate the efficacy of delamanid administered orally as 100 mg twice daily (BID) for 2 months followed by 200 mg once daily (QD) for 4 months in combination with an optimized background regimen (OBR) versus placebo with OBR during the 6-month intensive phase of MDR TB treatment. This trial is a multicenter, randomized, double-blind, stratified, placebo-controlled trial conducted globally in 2 parallel groups at approximately 18 sites in 7 countries qualified to treat MDR TB. In addition, a subtrial comprised of human immunodeficiency virus (HIV) positive patients who will be on antiretrovirals (ARVs) during the trial and will be randomized to OBR plus placebo or OBR plus delamanid will be conducted sites in South Africa that have been prequalified as having an integrated approach to TB and HIV treatment and management and a sufficient population of MDR TB patients co-infected with HIV for enrollment.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ECG
  • Cardiovascular disorders
  • BMI < 16 kg/m2
  • 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/metamphetamine, tetrahydrocannabinol, barbiturates, and opiates
  • Previous exposure to delamanid
  • Administered an IMP within 1 month prior to Visit 1
  • Evidence of XDR TB based on the definition from WHO
  • HIV co-infection for patients screened at sites not participating in the HIV subtrial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424670

Locations
Estonia
Tartu University Hospital, Lung Clinic
Tartu, Estonia, 51014
Latvia
State Agency "Infectology Center of Latvia" Clinic of Tuberculosis and Lung Diseases
Riga, Latvia, LV-2118
Lithuania
Public Institution Republican Siauliai Hospital Subsidiary Hospital of Tuberculosis and Lung Diseases
Siauliai, Lithuania, LT-76231
Infectious Diseases and Tuberculosis Hospital affiliate of Public institution Vilnius University Hospital
Vilnius, Lithuania, LT-10214
Moldova, Republic of
Public Medical Sanitary Institution Institute of Phtysiopneumology "Chiril Draganiuc" , MDR TB dept No.1
Chisinau, Moldova, Republic of
Peru
SERVICIO DE NEUMOLOGIA-Hospital Nacional Arzobispo Loayza, Av. Alfonso Ugarte 848
Lima, Lima 1, Peru
Hospital Nacional Hipolito Unanue, Avenida Cesar Vallejo 1390
Lima, Peru, 1390
Centro de Investigacion en Enfermedades Neumologicas - Hospital Nacional Sergio E. Bernales, Avenida Tupac Amaru Km 14.5, Urbanizacion Collique, Comas,
Lima, Peru, Lima 7
Unidad de Investigación Clinica - Servicio de Enfermedades Infecciosas y Tropicales - Hospital Nacional Dos de Mayo. Parque de la Medicina Peruana s/n, cuadra 13 Av. Grau. Cercado de Lima
Lima, Peru, Lima 1
Philippines
De La Salle University (DLSU), Angelo King Medical Research Center, Congressional Avenue
Dasmarinas City, Cavite, Philippines, 4114
Tropical Disease Foundation, Inc Philippine Institute of Tuberculosis Building. Amorsolo St. cor. Urban Ave., Pio del Pilar
Makati City, Manila, Philippines, 1230
Quezon Institute Compound, E. Rodriquez Avenue
Quezon City, Metro Manila, Philippines, 1101
Research and Development Office, 4th Floor, Room 4010, Lung Center Philippines, Quezon Avenue
Quezon City, Metro Manila, Philippines, 1104
South Africa
TASK Applied Science, Brooklyn Chest Hospital, 1 Stanberry Road, Ysterplaat, 7421,
Cape Town, Cape Town, Western Cape, South Africa, 7421
City Hospital
Durban, KwaZulu-Natal, South Africa, 4001
Head of the Department of Internal Medicine, Klerksdorp/Tshepong Hospital, Anderson Street, Klerksdorp
Klerksdorp,, South Africa, 2571, NORTH WEST
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Charles Wells, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01424670     History of Changes
Other Study ID Numbers: 242-09-213
Study First Received: August 25, 2011
Last Updated: June 29, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Multidrug resistant tuberculosis

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Multidrug-Resistant
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections

ClinicalTrials.gov processed this record on July 30, 2015