Evaluation of SQ109 Plus PPI in Urea Breath Test-Positive Volunteers
Evaluation of SQ109 Plus PPI in Urea Breath Test-Positive Volunteers
Helicobacter pylori infection of the gastric epithelium is the most common bacterial
 infection worldwide. Its global prevalence is estimated at 50%, though the burden falls
 disproportionately on the developing world, where the prevalence in some areas is 80%. H.
 pylori infection is generally acquired during childhood, and without specific antibiotic
 treatment can persist for life. The infection is generally clinically asymptomatic during
 childhood, and even in adulthood 80-90% of infected individuals will remain asymptomatic
 (although they may transmit the bacteria).

 SQ109 is a new, small molecule antibiotic with characteristics that make it particularly
 attractive to evaluate against H. pylori. In brief, SQ109 is orally bioavailable,
 acid-stable, has in vitro activity against H. pylori and achieves high intracellular
 concentration (which may be important to effect bacterial eradication).

 Based on the antimicrobial activity and clinical safety, SQ109 will be evaluated in this
 clinical trial to assess safety and antimicrobial activity in adults infected with H. pylori.
 Data from this study will help determine whether larger safety and efficacy studies in
 individuals with H. pylori-associated duodenal ulcer disease are warranted.
A total of 30 Urea Breath Test (UBT)-Positive volunteers will be enrolled. Each subject will
 receive SQ109 150 mg bid with PPI or 300 mg qd by mouth daily for 14 consecutive days.

 Major Inclusion/Exclusion Criteria:

 1. Subject must be 18 to 45 years of age (inclusive).

 2. Subject must have 2 positive Urea Breath Tests (UBT) obtaining during screening, and no
 other clinically significant disease (i.e., hematology, clinical chemistry and
 urinalysis tests must be within study-defined ranges. Clinical tests must be performed
 within 14 days of receiving first dose of study drug.

 3. Body Mass Index (BMI) must be between 18 and 33 kg/m2 inclusive.

 4. Subject must be able to give voluntary written informed consent before any study related
 procedure is performed.

 Objectives:

 1. To determine the safety and tolerability of SQ109 administered daily for 14 consecutive
 days in male and female Urea Breath Test (UBT)-positive subjects.

 2. To assess antimicrobial activity against H. pylori of SQ109 administered daily for 14
 days in UBT-positive subjects.

 Design: Each subject will undergo screening evaluations within 14 days of study entry (Day 1)
 and baseline evaluations Day -14 and Day -2 to Day 1 (up to 14 days prior to the first dose).
 On Day 1 (first day of dosing), the subject will be administered study drug and undergo the
 Day 1 procedures. Throughout the 14 days of treatment phase of the study each subject will be
 assessed daily for adverse events (AEs). Laboratory safety evaluations will be performed on
 Day 7, 8, 9, or 10, and on Day 14, and Day 21. On Days 1, 4, 7, 10, 14, 21, and 28 each
 subject will have a UBT. On Follow-up Days 21 and 28 each subject will return to the study
 unit to have safety assessments.

 Outcome Measures:

 Safety and tolerability will be evaluated by a review of physical examinations, neurological
 examinations, vital signs assessments, 12-lead ECGs, routine clinical laboratory tests
 (including chemistry and hematology data), and AE assessments.

 Efficacy Outcome Measures consist of serial UBT assessments for evidence of H. pylori in the
 gastrointestinal tract collected at baseline, during the 14 days of SQ109 administration, and
 during the 14 day follow-up period.
Major Inclusion Criteria:

 1. Subject must be 18 to 45 years of age (inclusive).

 2. Subject must have 2 positive Urea Breath Tests (UBT) obtaining during screening, and
 no other clinically significant disease (i.e., hematology, clinical chemistries and
 urinalysis tests must be within study-defined ranges (See Appendix B). Clinical tests
 must be performed within 14 days of receiving first dose of study drug.

 3. Body Mass Index (BMI) must be between 18 and 30 kg/m2 inclusive.

 4. Subject must be able to give voluntary written informed consent before any study
 related procedure is performed.

 5. If female, has no childbearing potential or agrees to avoid becoming pregnant from the
 day of screening through their entire participation in the trial (Day 42) by using one
 of the following acceptable methods of birth control plus recommended use of a barrier
 method (condom) by the male partner (even if vasectomized):

 1. intrauterine contraceptive device; or

 2. diaphragm in combination with contraceptive jelly, cream, or foam; or

 3. spermicide; or

 4. abstinence.

 Major Exclusion Criteria:

 1. A history of clinically significant gastrointestinal, renal, hepatic, neurologic,
 hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or
 cardiovascular disease or any other condition which would jeopardize the safety of the
 subject or impact the validity of the study results.

 2. Abnormal diet during the 4 weeks preceding the study.

 3. Use of any OTC or prescription medication, including vitamins and herbal supplements,
 within 7 days prior to Day 1 of the study, unless the substance would not likely
 impact on the conduct of this study.

 4. Current medical condition (other than H. pylori infection) requiring treatment with
 medication, either prescription or OTC.

 5. Treatment with any known CYP450 enzyme altering drugs such as azoles, antifungals,
 barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to
 Day 1 of the study.

 6. Positive blood screen for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C
 antibody and/or a positive urine screen for alcohol or drugs of abuse.

 7. Baseline QTc interval >450 msec (males) or >470 msec (females)or a family history of
 prolonged QTc syndrome or premature cardiac death.