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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01131351
Recruitment Status : Completed
First Posted : May 26, 2010
Last Update Posted : July 2, 2012
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary:

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 or disease Intervention/treatment Phase
Tuberculosis Drug: OPC-67683 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2010
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: OPC-67683
Dose Escalation
Drug: OPC-67683
Dosage-500-800 mg Strength 250-400 mg Frequency b.i.d.

Primary Outcome Measures :
  1. Vital signs [ Time Frame: 9 months ]
    blood pressure, heart rate, respiratory rate, body temperature and body weight

  2. Clinical Laboratory Assessments [ Time Frame: 9 months ]
    Hematology, chemistry, and urinalysis

  3. Standard 12-lead ECG [ Time Frame: 9 months ]
  4. Reported Adverse Events [ Time Frame: 9 months ]
  5. PK assessments [ Time Frame: 12 months ]
    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 :
  1. Sputum Culture Conversion [ Time Frame: 24 weeks ]
    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

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01131351

Infectology Center of Latvia - Clinic of Tuberculosis and Lung Diseases
Tinuzi Ogre District, Latvia, LV 5015
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.

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc. Identifier: NCT01131351     History of Changes
Other Study ID Numbers: 242-08-210
First Posted: May 26, 2010    Key Record Dates
Last Update Posted: July 2, 2012
Last Verified: June 2012

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

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