Safety, Tolerability and PK 3-Period Crossover Study Comparing 2 Single Doses of ZTI-01 and Monurol® in Healthy Subjects

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The objective is to determine the safety, tolerability and pharmacokinetics (PK) of 2 single doses of ZTI-01 (1g and 8g infused over 1-hr) and a single dose of the Reference Label Drug, Monurol® (oral sachet, 3g). Subjects will be randomized to a treatment sequence prior to dosing on Day 1 of Period 1 prior to study screening.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Fosfomycin

Criteria

Inclusion Criteria:

To be considered for study enrollment, subjects must meet all of the inclusion criteria:

• Healthy men and women from 18 to 45 years of age with no clinically significant findings on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) or clinical laboratory evaluation that were performed at Screening and Day -1.

• Body Mass Index (BMI) between 18-30 kg/m^2, inclusive; and a total body weight > 50 kg (110 lbs).

• Post-menopausal women with amenorrhea for at least 2 years with an FSH in the post-menopausal range as well as surgically sterile women (documented history of oophorectomy and/or hysterectomy, tubal ligation or tubal occlusion) will be eligible.

• Females of childbearing potential must use an acceptable birth control method (e.g., condom plus spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) throughout the study and for 4 weeks following initiation of dosing with study drug.

• Male subjects must either had a vasectomy or agree to use a double barrier method of contraception, condom plus spermicide (or diaphragm plus spermicide in female partner) from the time of dosing with the study drug in Period 1 through 4 weeks following initiation of dosing with study drug.

• Nicotine-free by history (cigarettes, pipe, cigar, chewing tobacco, nicotine patch) for at least 30 days before Day -1 and urine cotinine at pre-study screening and Day -1 <400 ng/mL).

• Able to abstain from grapefruit, grapefruit juice, grapefruit-containing products or alcoholic beverages within 48 hours before Day -1 and throughout the inpatient period.

• Willing to remain in the study facility and agree to abide to the Quintiles Phase 1 Unit House Rules for the duration of the inpatient study period.

• Have a high probability for compliance and completion of the study.

• Sign a dated, witnessed, written informed consent form

Exclusion Criteria:

Subjects must meet none of the following study criteria at Study Day -1, Period 1:

• History or presence of any psychiatric or emotional disorder that might prevent the successful completion of the study.

• Any surgical or medical condition that in the opinion of the investigator could interfere with drug absorption, distribution, metabolism, or excretion or any condition that may place the subject at increased risk while participating in the study. Examples of the conditions for exclusion: previous bariatric surgery, cardiovascular disease, renal impairment, renal disease, liver disease, chronic pulmonary disease, venous insufficiency, peripheral edema, borderline hypertension systolic pressure over > 140mmHg and or diastolic pressure >90 mmHg, serum sodium or liver enzymes above the upper limit, Regarding the last two conditions, one repeat is allowed at both screening and check-in to determine eligibility.

• Any history or presence of clinically significant allergic conditions (e.g., recurrent dermatitis or drug hypersensitivity reactions).

• Have cancer or have a history of cancer (with exceptions of a few types of cancer, e.g. recent removal of basal cell skin carcinoma) within the past five years.

• Irritable bowel syndrome or any gastrointestinal disease (including frequent nausea due to migraine) within 30 days prior to study day 1, Period 1.

• History or presence of lactose intolerance.

• History of alcohol abuse within 12 months of study day 1, Period 1.

• History of intolerance or hypersensitivity to phosphonic acid derivative antibiotics or any of its constituents

• Use of any prescription drugs within 30 days of administration of the study drug

• Involvement in other investigational studies of any type (drugs, devices, procedures) within 30 days of screening.

• Blood or blood products donation within 60 days of Day -1.

• Use of any non-prescription medications, vitamins, licorice (in large amounts) or dietary supplements within 7 days of administration of the study drug. Excluded from this list is intermittent use of acetaminophen at doses ofsupplements must be discontinued 7 days prior to the initial dose of study drug.

• Consumption of more than 300 mg of caffeine per day (>3 cups of coffee or 6-12 ounces of soda) within 7 days prior to dosing.

• Presence of any acute illness within 7 days of Day -1 in any Study Period.

• Breastfeeding or a positive serum pregnancy test at the Screening Visit or on Day -1 in any Study Period

• Positive tests for human immunodeficiency virus (HIV 1 and 2) antibodies, hepatitis B surface antigen (HBsAg) and/or hepatitis C (HCV) antibody.

• Positive urine drug or alcohol screen at the Screening Visit or on Day -1

• Weight loss or gain of > 10 percent within 30 days of Day -1.

• Females whose hemoglobin is <11.8 g/dL or males whose hemoglobin is <13.8g/dL.