Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB

NCT01218217 | Completed Phase 2

• 1 other identifier: LMU-IMPH-SQ109-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

SQ109 was developed with the aim of shortening TB treatment and providing new drugs for resistant TB. The drug has demonstrated efficacy in toxicology studies and an acceptable safety profile in first-in-man studies. The objective of this study is to evaluate the extended early bactericidal activity (EBA), safety, tolerability, and pharmacokinetics of several doses of SQ109 with or without Rifampicin (RIF) for 14 days in adults with newly diagnosed, uncomplicated, smear positive, pulmonary TB.

Conditions

Tuberculosis, Pulmonary

Keywords

TB; Tuberculosis; EBA; Pulmonary; Early Bactericidal Activity

Outcome Measures

Primary Outcomes (1)

• The extended early bactericidal activity (EBA)of daily 75 mg, 150 mg, and 300 mg SQ109, and of daily 150 mg or 300 mg SQ109 with daily RIF standard dose in adults with newly diagnosed, uncomplicated, smear positive, pulmonary TB.

  Daily during first two weeks

Secondary Outcomes (5)

• The standard EBA (EBA 0-2) of each treatment group, as determined by the rate of change of log Colony Forming Units (logCFU) in sputum over the period Day 0-2 (linear, bi-linear or non-linear regression of logCFU over time).

  Day 0 - Day 2

• Extended EBA (EBA 2-14) of each treatment group, as determined by the rate of change of logCFU in sputum over the periods Day 2-14 (linear, bi-linear or non-linear regression of logCFU over time).

  Days 2-14

• The change in time to positivity (TTP) in the Mycobacterium Growth Indicator Tube (Bactec MGIT 960 system).

  Days 0-14

• Pharmacokinetics

  Days 1,2,7,8,14,15

• Proportion of subjects with serious adverse events and proportion of subjects who discontinue due to an adverse event in each experimental arm.

  Entire study period

Study Arms (6)

SQ109 75 mg

EXPERIMENTAL

75 mg SQ109 monotherapy daily

Drug: SQ109

SQ109 150 mg

EXPERIMENTAL

150 mg SQ109 daily

Drug: SQ109

SQ109 300 mg

EXPERIMENTAL

300 mg SQ109 daily

Drug: SQ109

SQ109 150 mg + RIF

EXPERIMENTAL

150 mg SQ109 + RIF standard dose daily

Drug: SQ109; Drug: Rifampicin

SQ109 300 mg + RIF

EXPERIMENTAL

300 mg SQ109 + RIF standard dose daily

Drug: SQ109; Drug: Rifampicin

RIF Mono

ACTIVE COMPARATOR

Standard dose Rifampicin monotherapy daily

Drug: Rifampicin

Interventions

SQ109 DRUG

SQ109 150 mg tablet

SQ109 150 mg; SQ109 150 mg + RIF; SQ109 300 mg; SQ109 300 mg + RIF; SQ109 75 mg

Rifampicin DRUG

Rifampicin 150 mg capsules

RIF Mono; SQ109 150 mg + RIF; SQ109 300 mg + RIF

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provide signed written informed consent for study participation, including HIV testing (if HIV serostatus is not known or the last documented negative is more than four weeks prior to enrolment).
• Be eighteen (18) to 64 (inclusive) years of age.
• Have a body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
• Have newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary TB.
• Have a chest X-ray which, in the opinion of the Investigator, is compatible with TB.
• Is sputum positive on direct microscopy for acid-fast bacilli (at least 1+ on the IUATLD/WHO scale (Appendix 3).
• Is able to produce an adequate spot sputum sample, indicating an overnight sputum volume of at least 10 mL.
• Female patients of childbearing potential must have a negative serum pregnancy test, and consent to practice two effective methods of birth control when not abstaining from sexual intercourse, unless she and her partner(s) are surgically sterile or she is post-menopausal with no menses for the last 12 months. Preferably, contraceptive measures should be continued until completion of TB treatment, but at least until one month after last dose of IMP, unless she and her partner(s) are sterile (that is, women who have had a bilateral oophorectomy or hysterectomy or have been postmenopausal for at least 12 consecutive months).
• Two of the following methods may be used, but only one may be hormonal: tubal ligation, vaginal diaphragm, intrauterine device, condom, oral contraceptives, contraceptive implant, combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate, partner(s) has had a vasectomy.
• Male participants must agree to use an adequate method of contraception when not abstaining from sexual intercourse throughout participation in the trial and for 12 weeks after last dose, unless he has had bilateral orchidectomy.
• A Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs, see Appendix 5)

You may not qualify if:

• Poor general condition where any delay in treatment cannot be tolerated per discretion of Investigator.
• Treatment with any drug active against MTB within the 3 months prior to Visit 1 (this includes, but is not limited to INH, EMB, RIF, PZA, amikacin, cycloserine, rifabutin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, thioacetazone, capreomycin, fluoroquinolone, thioamides, metronidazole).
• Sputum isolate is resistant to RIF as detected by rapid assay from native sputum
• A history of allergy to the IMP or related substances.
• Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the investigator.
• A history of previous TB.
• Evidence of serious lung conditions other than TB or uncontrolled obstructive bronchial disease.
• Laboratory parameters done at, or within 14 days prior to, screening:
• Serum amino aspartate transferase (AST) and/or serum alanine aminotransferase (ALT) activity \>3 times the upper limit of normal
• Serum total bilirubin level \>2.5 times the upper limit of normal
• Serum creatinine level \>2 times the upper limit of normal
• Complete blood count with hemoglobin level \<7.0 g/dL
• Platelet count \<50,000/mm3
• Serum potassium \<3.5 meq/L
• History, presence, or evidence of a neuropathy or epilepsy.

Sponsors & Collaborators

• Michael Hoelscher: lead
• Sequella, Inc.: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• German Federal Ministry of Education and Research: collaborator
• Quintiles, Inc.: collaborator
• CMed Technologies Inc.: collaborator
• PathCare: collaborator
• Parexel: collaborator

Study Sites (2)

TASK Applied Sciences

Cape Town, South Africa

Location

University of Cape Town

Cape Town, South Africa

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Michael Hoelscher, MD

  Klinikum of the University of Munich

  STUDY CHAIR

• Andreas Diacon, MD

  Task Applied Sciences

  PRINCIPAL INVESTIGATOR

• Rodney Dawson, MD

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 11, 2010
• Study Start: November 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: May 1, 2012
• Last Updated: January 14, 2013

Record last verified: 2013-01

Locations

ZA (2)