Safety and Pharmacokinetics (PK) in Multidrug-Resistant (MDR) Refractive Tuberculosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01131351
First received: May 25, 2010
Last updated: June 26, 2012
Last verified: June 2012
  Purpose

The purpose of this study is:

  • To evaluate the safety and tolerability of orally administered OPC-67683 when administered two times daily (BID) to MDR TB patients refractory to treatment with an optimized background regimen of anti-TB medications (OBR).
  • To evaluate the pharmacokinetics (PK) of OPC-67683 and metabolites.

Condition Intervention Phase
Tuberculosis
Drug: OPC-67683
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-center, Non-controlled, Open-label Dose Escalation Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of Orally Administered OPC-67683 Two Times Daily to Patients With Pulmonary Multidrug-Resistant Tuberculosis Refractory to Conventional Treatment

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Vital signs [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    blood pressure, heart rate, respiratory rate, body temperature and body weight

  • Clinical Laboratory Assessments [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    Hematology, chemistry, and urinalysis

  • Standard 12-lead ECG [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • Reported Adverse Events [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • PK assessments [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Pharmacokinetics parameters including maximum observed plasma concentration (Cmax), time to maximum plasma concentration (tmax), lowest plasma concentration during the 24 hours postdose (Cmin), and area under the plasma concentration-time curve from time 0 to 24 hours (AUC0-24h) at various time points.


Secondary Outcome Measures:
  • Sputum Culture Conversion [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Efficacy evaluation of sputum culture conversion including proportion of patients with sputum culture conversion at Day 168 evaluated with MGIT® culture system and solid media


Enrollment: 10
Study Start Date: February 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OPC-67683
Dose Escalation
Drug: OPC-67683
Dosage-500-800 mg Strength 250-400 mg Frequency b.i.d.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provide written, informed consent prior to all trial-related procedures
  2. Male or female patients aged between 18 and 64 years, inclusive.
  3. Able to produce sputum for mycobacterium culture or able to obtain sputum produced through Induction.
  4. At least three sputum mycobacterium cultures positive for MTB with in-vitro resistance to isoniazid and rifampicin during the previous 270 days (9 months) despite treatment with first and second line anti-TB drugs, including one positive culture within the previous 60 days from the time of sputum collection, prior to date of screening initiation (defined as the date the ICF is signed and screening begins).
  5. Sputum mycobacterial culture positive for MTB with in-vitro susceptibility to at least one anti-TB Medication within the previous 60 days prior to the date of screening initiation.
  6. Patient judged by the investigator to have potential for clinical benefit from OPC-67683 exposure.
  7. Female patients of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control (for example, two of the following precautions: tubal ligation, vaginal diaphragm, intrauterine device, oral contraceptives, contraceptive implant,combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate) throughout the participation in the trial and for 22 weeks after last dose (to cover duration of ovulation).
  8. Male patients must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30 weeks after last dose (to cover duration of spermatogenesis.

Exclusion Criteria:

  1. A history of allergy to any nitro-imidazoles or nitro-imidazole derivatives at any time.
  2. Use of the medications in Section 4.1 including: use of amiodarone at any time during the previous 12 months, use of other anti-arrhythmics for the previous 30 days, as well as use of certain antidepressants, Anti-histamines, any macrolides, for the previous 14 days.
  3. Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels ≥265 μmol/L or hepatic impairment characterized by ALT and/or aspartate transferase (AST)levels 3 times the upper limit of the laboratory reference range.
  4. Current clinically relevant changes in the Screening ECG such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 msec (in both male and female patients), or of the QTcF interval over 450 msec in male patients and over 470 msec in female patients.
  5. Current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease,uncontrolled or poorly controlled hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction.
  6. For patients with HIV infection, CD4 cell count < 350/mm3 or on treatment with anti-retroviral medication for HIV infection.
  7. Karnofsky score < 50%.
  8. Any current diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01131351

Locations
Latvia
Infectology Center of Latvia - Clinic of Tuberculosis and Lung Diseases
Tinuzi Ogre District, Latvia, LV 5015
Lithuania
Hospital for Tuberculosis and Lung Diseases
Siauliai, Lithuania, LT-76231
National Tuberculosis and Infectious Diseases University Hospital
Vilnius, Lithuania, LT-10214
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01131351     History of Changes
Other Study ID Numbers: 242-08-210
Study First Received: May 25, 2010
Last Updated: June 26, 2012
Health Authority: United States: Food and Drug Administration
Latvia: State Agency of Medicines of Republic of Latvia (SAM) & European Commission (EC)
Lithuania: State Medicines Control Agency (SMCA) & European Commission (EC)

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
MDR-TB
Dose Escalation
Phase II
Open Label
Non Controlled
Pulmonary Multidrug-Resistant Tuberculosis (MDR TB)

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

ClinicalTrials.gov processed this record on April 16, 2014