Safety & Tolerability of a Combination of Antidepressant and Peptic Ulcer Drug in Overweight Healthy Subjects
Condition: Obesity
MeSH terms: Overweight
Intervention: Sertraline plus Telenzepine
Intervention description: oral sertraline tablets at 0, 50, 100, or 150/day plus oral telenzepine capsules at 0, 1, 2, or 3 mg/day for 7 days in each combination
Intervention MeSH terms: Sertraline; Telenzepine
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Obesity; Overweight; Sertraline; Telenzepine; Decrease appetite; Reduce appetite; Lose weight

Summary:

      The hypothesis of this study is that up to 150 mg of sertraline and up to 3 mg of telenzepine
      will be safe, tolerable, and have the effect of suppressing appetite, when taken in
      combination daily by mouth by healthy, overweight, adult men and women.

      In this study, up to 12 people will be assigned to one of 4 groups: A, B, C, and D, and will
      receive 0, 50, 100, or 150 mg of sertraline per day. People in Groups B, C, or D will receive
      an initial dose of 50 mg sertraline. People in Groups C and D will receive an additional 50
      mg of sertraline per week.

      Up to 10 people from each group who were able to tolerate their sertraline dose for at least
      5 days will begin taking 50 mg of sertraline plus doses of telenzepine that will increase
      from 1 mg to 2 mg to 3 mg over a 7-day period (they will receive each combination). On the
      day before they begin taking this combination of drugs, their appetite will be evaluated (on
      a visual scale of 0 to 100) before and after 3 meals.

      The appetites of each person, assessed by the visual scale, will be evaluated on the last day
      of the period (Day 7) before and after 3 meals of each combination treatment, while they are
      staying in the research unit. The amount of food they eat will be determined.

      Based on safety and tolerability assessments of individuals, and of the previous groups who
      received lower doses of the combination of drug, a decision will be made whether to further
      increase the dose of these drugs.

      Since the appetites of each person will be evaluated on the last day of the period (Day 7)
      before and after 3 meals of each combination treatment, people in this study will stay in the
      research unit for approximately 2½ days, starting on Day 6 of their previous treatment, so
      appetite evaluations can be made on Day 7 after a fixed meal in the evening of Day 6. These
      people will continue the stay in the research unit when they begin each telenzepine dose
      increase, so a 24 hour safety observation may be made immediately after the increase.

      After the final doses of telenzepine have been received, people in Groups C and D will
      continue to receive sertraline 50 mg per day for an additional 7 days or until the study
      physician decides when sertraline should be discontinued. People will return to the study
      unit for final visit, 2 weeks after they have received their last sertraline dose.
    

Eligibility criteria:

        Inclusion Criteria:

          -  In good health based on medical history, physical examination, ECG, routine laboratory
             tests, and BMI >/= 30 kg/m2 and </=30 40 kg/m^2.

          -  Males and females agree to use described birth control methods.

          -  Non-smoker.

          -  Willing and able to be confined to the clinical research facility.

          -  Willing and able to comply with the protocol and able to communicate with
             investigators.

          -  Able to comprehend and willing to provide written informed consent.

        Exclusion Criteria:

          -  Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease
             (including drug allergies; patients with untreated, asymptomatic, seasonal allergies
             may be enrolled), surgical conditions, cancer or any other condition that might in the
             opinion of the investigator impair the ability of the subject to complete the study or
             significantly interfere with the absorption, distribution, metabolism, or excretion of
             the study drugs.

          -  Evidence or history of clinically significant psychiatric disease including major
             depression, mania, or hypomania, and history of suicide attempts or suicidal ideation.
             Subjects with a Beck Depression Inventory-II (BDI-II) score >13 at screening are
             excluded.

          -  Clinically relevant abnormal findings at the screening examination (including
             laboratory tests and ECG).

          -  Screening ECG which demonstrates at least one of the following: heart rate > 100 bpm,
             QRS > 120 msec, QTc > 450 msec, PR > 220 msec or any rhythm other than sinus rhythm,
             sinus bradycardia, or sinus arrhythmia.

          -  Change in weight > 5 kilograms within 3 months of screening.

          -  History of alcohol consumption exceeding 14 drinks/week (1 drink equaling 5 ounces of
             wine, 12 ounces of beer, or 1.5 ounces of hard liquor) within the 6 months before
             study entry.

          -  Sitting systolic blood pressure ≤90 millimeters of mercury (mmHg) or ≥140 mmHg,
             diastolic blood pressure </= 50 mmHg or >/= 90 mmHg and judged to be clinically
             significant by the investigator.

          -  Positive result on drug screen, hepatitis B surface antigen (HBsAg), hepatitis C
             (HCV), or human immunodeficiency (HIV) tests.

          -  Use of prescription or non-prescription drugs, vitamins, or dietary supplements within
             14 days prior to the first dose of study medication. Subjects on oral contraceptives
             and subjects who have used acetaminophen at doses of < 2 grams/day are eligible for
             study entry. Any exception to this must be felt not to impact the integrity of the
             data and must be jointly agreed upon by the investigator and medical monitor.

          -  Treatment with any investigational drug, use of any known CYP450 enzyme-
             inducing/inhibiting agents (e.g., barbiturates, phenothiazines, cimetidine, St. John's
             Wort) or herbal supplements within 30 days prior to the first dose of study
             medication.

          -  Treatment with any psychotropic medication within 90 days of screening.

          -  History of drug abuse or dependence within 180 days of screening.

          -  Febrile illness within 5 days prior to the first dose of study medication.

          -  Inadequate venous access.

          -  Known allergy to sertraline or telenzepine.

          -  History of an active eating disorder such as anorexia nervosa, bulimia or binge eating
             disorder.

          -  Elevated ALT (> 2X ULN) or total bilirubin (> 1.6 mg/dL)

          -  Have diabetes mellitus (fasting plasma glucose > 126 mg/dL)

          -  Have been on weight loss medications in the past 6 months