A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)
NCT ID: NCT01859923
Last Updated: 2020-11-23
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
37 participants
INTERVENTIONAL
2013-07-20
2020-01-13
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Group 1: 12 to 17 Years of Age
Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) plus optimized background regimen (OBR) up to Day 182. Participants continued to receive OBR up to Day 365.
Delamanid
Participants received adult formulation delamanid as per regimen specified in the arm description. Morning dose of the delamanid BID regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard dinner meal.
Optimized Background Regimen (OBR)
Selection and administration of the treatment medications (i.e. OBRs) was based on Search Results Web result with site links
World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study Investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Group 2: 6 to 11 Years of Age
Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Delamanid
Participants received adult formulation delamanid as per regimen specified in the arm description. Morning dose of the delamanid BID regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard dinner meal.
Optimized Background Regimen (OBR)
Selection and administration of the treatment medications (i.e. OBRs) was based on Search Results Web result with site links
World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study Investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Group 3: 3 to 5 Years of Age
Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Delamanid Pediatric Formulation (DPF)
Participants received delamanid as an extemporaneous suspension using the delamanid pediatric dispersible tablet formulation. Morning dose of the delamanid BID/once daily (QD) regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard meal.
Optimized Background Regimen (OBR)
Selection and administration of the treatment medications (i.e. OBRs) was based on Search Results Web result with site links
World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study Investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Group 4: Birth to 2 Years of Age
Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit:
* Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR
* Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR
* Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR
Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Delamanid Pediatric Formulation (DPF)
Participants received delamanid as an extemporaneous suspension using the delamanid pediatric dispersible tablet formulation. Morning dose of the delamanid BID/once daily (QD) regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard meal.
Optimized Background Regimen (OBR)
Selection and administration of the treatment medications (i.e. OBRs) was based on Search Results Web result with site links
World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study Investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Interventions
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Delamanid
Participants received adult formulation delamanid as per regimen specified in the arm description. Morning dose of the delamanid BID regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard dinner meal.
Delamanid Pediatric Formulation (DPF)
Participants received delamanid as an extemporaneous suspension using the delamanid pediatric dispersible tablet formulation. Morning dose of the delamanid BID/once daily (QD) regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard meal.
Optimized Background Regimen (OBR)
Selection and administration of the treatment medications (i.e. OBRs) was based on Search Results Web result with site links
World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study Investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Confirmed diagnosis of MDR-TB OR
* Presumptive diagnosis of pulmonary or extrapulmonary MDR-TB including one of the following:
* Clinical specimen suggestive of tuberculosis disease
* Persistent cough lasting \> 2 weeks
* Fever, weight loss, and failure to thrive
* Findings on recent chest radiograph (prior to Visit 1) consistent with TB AND
* Household contact with a person with known MDR-TB or with a person who died while appropriately taking drugs for sensitive TB OR
* On first-line TB treatment but with no clinical improvement
* Negative urine pregnancy test for female participants who have reached menarche
* Written informed consent/assent
Exclusion Criteria
* Laboratory evidence of active hepatitis B or C
* Children with body weight \< 5.5 kg
* For participants with human-immunodeficiency virus (HIV) co-infection, cluster difference-4 (CD4) cell count ≤ 1000/mm\^3 for children 1-5 years old, and ≤ 1500/mm\^3 for children less than 1 year old
* History of allergy to metronidazole and any disease or condition in which metronidazole is required
* Use of amiodarone within 12 months or use of other predefined antiarrhythmic medications within 30 days prior to first dose of delamanid
* Serious concomitant conditions
* Pre-existing cardiac conditions
* Abnormalities in Screening electrocardiogram (ECG) \[including atrio-ventricular (AV) block, blood brain barrier (BBB) or hemi-block, QRS prolongation \> 120 milliseconds (ms), or QT interval corrected by Fridericia's formula (QTcF) \> 450 ms in both males and females\]
* Concomitant condition such as renal impairment characterized by serum creatinine levels \> 1.5 mg/dL, hepatic impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3x upper limit of normal (ULN)), or hyperbilirubinemia characterized by total bilirubin \> 2x ULN
* Current diagnosis of severe malnutrition or kwashiorkor
* Positive urine drug screen (Groups 1 and 2 only)
* Rifampicin and/or moxifloxacin within 1 week prior to the first dose of delamanid and/or any prior or concurrent use of bedaquiline
* Lansky Play Performance Score \< 50 (not applicable for children \< 1 year old) or Karnofsky Score \< 50
* Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 other than delamanid given as IMP in Trial 242-12-232
* Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form (Groups 1 and 2 only)
0 Years
17 Years
ALL
No
Sponsors
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Otsuka Pharmaceutical Development & Commercialization, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Melchor VG Frias, IV, MD
Role: PRINCIPAL_INVESTIGATOR
De La Salle Health Sciences Institute
Anjanette Reyes-De Leon, MD
Role: PRINCIPAL_INVESTIGATOR
Lung Center of the Philippines
Louvina van der Laan, MD
Role: PRINCIPAL_INVESTIGATOR
Brooklyn Chest Hospital
Locations
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De La Salle Health Sciences Institute
Dasmariñas, Cavite, Philippines
Lung Center of the Philippines
Quezon City, National Capital Region, Philippines
Brooklyn Chest Hospital
Ysterplaat, Cape Town, South Africa
Countries
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References
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Garcia-Prats AJ, Frias M, van der Laan L, De Leon A, Gler MT, Schaaf HS, Hesseling AC, Malikaarjun S, Hafkin J. Delamanid Added to an Optimized Background Regimen in Children with Multidrug-Resistant Tuberculosis: Results of a Phase I/II Clinical Trial. Antimicrob Agents Chemother. 2022 May 17;66(5):e0214421. doi: 10.1128/aac.02144-21. Epub 2022 Apr 11.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2012-004620-38
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
242-12-233
Identifier Type: -
Identifier Source: org_study_id