NCT01424670

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
511

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Sep 2011

Longer than P75 for phase_3

Geographic Reach
7 countries

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 25, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 29, 2011

Completed
4 days until next milestone

Study Start

First participant enrolled

September 2, 2011

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 4, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 4, 2016

Completed
2.9 years until next milestone

Results Posted

Study results publicly available

May 15, 2019

Completed
Last Updated

May 15, 2019

Status Verified

May 1, 2019

Enrollment Period

4.8 years

First QC Date

August 25, 2011

Results QC Date

October 9, 2018

Last Update Submit

May 13, 2019

Conditions

Multidrug-resistant Tuberculosis

Keywords

Multidrug-resistant tuberculosis

Outcome Measures

Primary Outcomes (1)

  • Time To Sputum Culture Conversion (SCC) During 6-Month Intensive Period Using The Mycobacteria Growth Indicator Tube (MGIT) System

    SCC at 6 months was determined by the observation of a sputum specimen negative for growth of mycobacterium tuberculosis (MTB) using the MGIT culture system, followed by at least 1 confirmatory negative sputum culture at least 25 days after the first negative and not followed by a confirmed positive (defined as at least 2 observed positive results, not taking into account indeterminate, missing, or contaminated results). 2 specimens were collected at each visit and an algorithm in the statistical analysis plan (SAP) was used to define a single representative result. Time to SCC was then defined as the interval between the date of first dose of IMP and the date of first of 2 consecutive negative single representative time points that were at least 25 days apart. The median time in days to SCC up to Month 6 is presented.

    Month 6

Secondary Outcomes (7)

  • Proportion of Participants With SCC At 2 And 6 Months Using MGIT

    Month 2 and Month 6

  • Proportion of Participants With Sustained SCC At Month 18, Month 24, And Month 30 Using MGIT

    Month 18, Month 24, and Month 30

  • Treatment Outcomes Assessed By Principal Investigators (PI)At The End Of Treatment With OBR

    Month 24

  • Number of Participants Who Developed Resistance To Delamanid

    Up to Month 30

  • Mean (Time Averaged) Area Under The Curve (AUC) Of Change From Baseline In Time To Detection (TTD) To Month 6 Using MGIT

    Baseline, up to Month 6

  • +2 more secondary outcomes

Study Arms (2)

Delamanid + OBR

EXPERIMENTAL

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.

Drug: Delamanid + OBR

Placebo + OBR

PLACEBO COMPARATOR

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.

Drug: Placebo + OBR

Interventions

Delamanid + OBRDRUG

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.

Delamanid + OBR
Placebo + OBRDRUG

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.

Placebo + OBR

Eligibility Criteria

Age18 Years - 69 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Unknown Facility

Tartu, 51014, Estonia

Location

Unknown Facility

Riga, LV-2118, Latvia

Location

Unknown Facility

Å iauliai, LT-76231, Lithuania

Location

Unknown Facility

Vilnius, LT-10214, Lithuania

Location

Unknown Facility

Chisinau, MD2025, Moldova

Location

Unknown Facility

Vorniceni, MD3737, Moldova

Location

Unknown Facility

Alfonso Ugarte, Lima 1, Peru

Location

Unknown Facility

Comas, Lima 7, Peru

Location

Unknown Facility

El Agustino, Lima 10, Peru

Location

Unknown Facility

Lima Cercado, Lima 1, Peru

Location

Unknown Facility

Dasmariñas, Cavite, 4114, Philippines

Location

Unknown Facility

Quezon City, National Capital Region, 1104, Philippines

Location

Unknown Facility

Makati City, 1230, Philippines

Location

Unknown Facility

Quezon City, 1101, Philippines

Location

Unknown Facility

Cape Town, 7405, South Africa

Location

Unknown Facility

Durban, 4001, South Africa

Location

Unknown Facility

Klerksdorp, 2571, South Africa

Location

Related Publications (1)

  • 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.

    PMID: 30630778DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

OPC-67683

Condition Hierarchy (Ancestors)

TuberculosisMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Limitations and Caveats

The primary endpoint was established at 6 months. Treatment, intensive data collection, and statistical power calculations focused on the first 6 months. Given the unexpected placebo + OBR response, cautiously interpret 18, 24, and 30 month outcomes.

Results Point of Contact

Title
Global Clinical Development
Organization
Otsuka Pharmaceutical Development & Commercialization, Inc.
clinicaltransparency@otsuka-us.com
+1-609-524-6788

Study Officials

  • Global Clinical Development

    Otsuka Pharmaceutical Development & Commercialization, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 25, 2011

First Posted

August 29, 2011

Study Start

September 2, 2011

Primary Completion

July 4, 2016

Study Completion

July 4, 2016

Last Updated

May 15, 2019

Results First Posted

May 15, 2019

Record last verified: 2019-05

Locations

PH(4)ZA(3)LA(1)LI(2)MO(2)PE(4)ES(1)