Phase 2
Completed N=37
A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)
Source: ClinicalTrials.gov NCT01859923 ↗Enrolled (actual)
37
Serious AEs
21.6%
Results posted
Nov 2020
Primary outcomePrimary: Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) — 7; 6; 12; 12 Participants
Summary
The purpose of this trial is to assess the safety, tolerability, pharmacokinetics, and efficacy of long-term (6-month) treatment with delamanid plus an optimized background regimen (OBR) of other anti-tuberculosis drugs in pediatric participants who completed Study 242-12-232 (NCT01856634).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) |
7; 6; 12; 12 | — |
| PRIMARY Number of Participants With Abnormal Physical Examination Values |
1; 1; 4; 2; 2; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormal Vital Sign Values |
0; 2; 0; 1; 4; 2 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values |
1; 0; 1; 4; 1; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Test Abnormalities |
0; 0; 0; 1; 1; 0 | — |
| PRIMARY Population Pharmacokinetic (POPPK) Model Point Estimate for Central Clearance (L) and Inter-compartmental Clearance (Q) of Delamanid |
18.1; 105 | — |
| PRIMARY POPPK Model Point Estimate for Central Volume of Distribution (Vc) and Peripheral Volume of Distribution (Vp) of Delamanid |
254; 347 | — |
| PRIMARY POPPK Model Point Estimate for Absorption Rate Constant (Ka) of Delamanid |
0.254 | — |
| PRIMARY POPPK Model Point Estimate for Absorption Lag Time (ALAG1) of Delamanid |
1.38 | — |
| SECONDARY Baseline QT Interval (QTcB) Effect |
0.0318; 0.0309 | — |
| SECONDARY PK/PD Relationship: POPPK Model Point Estimate for Slope of Linear Mixed Effects Model for Change in QTcB Interval Versus Delamanid Plasma Concentrations |
0.00792; 0.0613 | — |
| SECONDARY Number of Participants With Treatment Outcome as Assessed by Principal Investigator |
6; 6; 10; 11; 1; 0 | — |
| SECONDARY Number of Participants With Abnormal Chest X-ray |
7; 6; 12; 11 | — |
| SECONDARY Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis |
6; 4; 3; 7; 1; 2 | — |
| SECONDARY Sputum Culture Conversion (SCC) |
— | — |
| SECONDARY Number of Participants With Palatability Score as Assessed by the Investigator |
0; 0; 0; 2; 1; 0 | — |
| SECONDARY Number of Participants With Palatability Score as Assessed by the Parent or Participant |
0; 0; 0; 1; 1; 1 | — |
Eligibility Criteria
Inclusion Criteria
- Successfully completed Trial 242-12-232
- 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
- Participants who have not completed Trial 242-12-232
- Laboratory evidence of active hepatitis B or C
- Children with body weight 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)
Data sourced from ClinicalTrials.gov (NCT01859923). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.