Clinical trial NCT01597609 (phase 1, status: completed)
Conditions: obesity
ICD codes: E66.8, E66.9, E66.1, O99.214, O99.215, O99.210, O99.211
Drugs: sibutramine
SMILES: CC(C)CC(N(C)C)C1(CCC1)C1=CC=C(Cl)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Subject is a healthy male or female adult subject aged 20 to 55 years, inclusive.

        Subjects will be allowed in the study if they have medical conditions, such as asthma,
        which will not compromise the validity of the study in the opinion of the Principal
        Investigator and Medical Advisor.

          -  BMI within the range 30.0 to 40.0 kg/m2 inclusive.

          -  Has been obese from approximately the age of 18 or above.

          -  Has demonstrated previous weight loss sustained for a minimum of one month.

          -  Pre-menopausal female subjects of child bearing potential who are not pregnant or
             breast feeding will be eligible to participate if they comply with the following:
             Abstinence.

        The lifestyle of female subjects should be such that there is complete abstinence from
        intercourse from at least 30 days prior to receiving study medication and to continue until
        30 days beyond the last study event, or 5 half lives of the study medication, whichever is
        the longest. If a subject claims abstinence as their method of contraception, they must
        agree to use a double barrier method (condoms, cervical/vault cap or diaphragm plus
        spermicide) should they become sexually active during the time frame described above. One
        of the following methods is acceptable as the sole method of contraception if there is
        indisputable data that it is >99% effective, otherwise it should be used with a barrier
        method (condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicidal
        foam/gel/film/cream/suppository): Documented tubal ligation, IUD or IUS, Oral
        contraception, Male partner sterilization (vasectomy) at least 6 months prior to the female
        subject's entry into the study and is the sole partner for that female subject. Condom or
        occlusive cap (diaphragm or cervical/vault caps) with spermicidal
        foam/gel/film/cream/suppository (Appendix 3).

          -  Subject has provided signed and dated, written informed consent prior to enrolment in
             the study.

          -  The subject is able to understand and comply with protocol requirements, instructions,
             and protocol-stated restrictions.

        Exclusion Criteria:

          -  Has either a previous disease or current medical condition, which as judged by the
             Investigator, may affect the interpretation of data. These diseases include, but are
             not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease,
             haematological disease, neurological disease or endocrine disease.

          -  Currently has closed angle glaucoma.

          -  Has prostatic hypertrophy or hyperplasia.

          -  Females who are post-menopausal (post-menopausal females defined as being amenorrhoeic
             for more than 2 years with an appropriate clinical profile, e.g. history of vasomotor
             symptoms and confirmed by an FSH ≥ 40 mIU/mL).

          -  Known history of panic attacks and/or claustrophobia or other conditions precluding
             safe DEXA and Echo MRI-AH scans according to local guidelines, (e.g., pacemaker,
             hearing aid, metallic body piercing and/or other metal implants) or in the opinion of
             the Investigator the subject exceeds size limitations for the instruments.

          -  Has a history of clinically significant eating disorders (diagnosed and/or treated)
             such as previous anorexia nervosa, binge-eating disorder or bulimia nervosa.

          -  Has a recent history of weight loss (or gain) defined as a change of ≥ 5 % in the 3
             months prior to screening.

          -  Has a history of being obese in childhood.

          -  Has had bariatric surgical intervention for obesity.

          -  Has a confirmed diagnosis of polycystic ovary syndrome.

          -  Has a history of alcohol or substance abuse or dependence in the 6 months prior to
             screening as determined by the Investigator. Abuse of alcohol, defined for males, as
             an average weekly intake of greater than 21 units (or an average daily intake of
             greater than 3 units), or defined for females, as an average weekly intake of greater
             than 14 units (or an average daily intake of greater than 2 units). One unit is
             equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits or 1 glass
             (125mL) of wine.

          -  Subjects will not be eligible if they plan to alter their current smoking (or other
             tobacco use) status during the course of the study, or if they have quit smoking less
             than 3 months prior to screening. Because of the effects of tobacco smoke on
             biomarkers, subjects may be classified as 'never smokers' or 'current smokers
             (abstaining at study visit) + former smokers'.

          -  Subjects who could not refrain from smoking during the time of the visit in the unit.

          -  Has a positive urine drug test at screening or pre-intervention. At a minimum,
             subjects will be screened for amphetamines, barbiturates, cocaine, opiates,
             cannabinoids, and benzodiazepines, and may be screened randomly throughout the study.

          -  Positive results for hepatitis C antibodies, hepatitis B surface antigen, or HIV at
             screening. If negative results have been obtained in the last 6 months, it is not
             necessary to repeat the tests unless indicated by clinical judgment.

          -  Has a documented history of hepatobiliary disease or hepatic enzyme elevation
             including any one of the following: ALT or AST > 2.5 times the upper limit of normal
             at screening or pre-intervention Total bilirubin > 1.5 times the upper limit of normal
             at screening or pre-intervention.

        Subjects above this limit may only be included if direct bilirubin is within normal limits,
        which would be consistent with Gilbert's disease.

          -  Fasting triglycerides > 600mg/dL at screening or pre-intervention. If receiving
             lipidlowering therapy, then the subject must have been on stable doses for at least 3
             months prior to screening.

          -  Has known type 1 or type 2 diabetes mellitus; or has fasting plasma glucose ≥ 126mg/dL
             (7.0 mmol/L) at screening. Subjects who fall outside this range but below 140 mg/dL
             fasting will be evaluated for inclusion by the PI or designee.

          -  Has a thyroid disorder that is not under adequate control with a stable dose of
             hormone replacement for at least 3 months prior to screening. Inadequate control is
             defined as a TSH level below the lower limit of the reference range (LLRR) or > 1.5

             × ULRR at screening.

          -  Has a systolic BP above 150 mmHg and/or diastolic BP above 90 mmHg at screening. If
             receiving anti-hypertensive therapy, then the subject must have been on stable doses
             for at least 3 months prior to screening.

          -  Is incapable or unwilling to participate in a moderate walking exercise program.

          -  Is pregnant or planning a pregnancy in the following 27 weeks from screening.

          -  Has any clinically significant abnormality identified on the medical or laboratory
             evaluation, including 12-lead ECG. A subject with a clinically significant abnormality
             or laboratory parameters outside the reference range for this age group may be
             included only if the Investigator considers that the finding will not introduce
             additional risk factors and will not interfere with the study procedures. Any
             questions regarding the significance of abnormal clinical findings in screening
             results should be discussed with the GSK Medical Monitor.

          -  Exclusions relating to concomitant preparations and medications: use of prescription
             or non-prescription drugs, including vitamins, herbal and dietary supplements
             (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme
             inducer) or 5 half-lives (which ever is longer) prior to the first dose of study
             medication, unless in the opinion of the Investigator and Sponsor the medication will
             not interfere with the study procedures or compromise subject safety.

          -  Planning to commence or stop HRT or oral contraceptives during the course of the
             study. Female subjects who are taking an oral contraceptive preparation at the time of
             screening may be eligible for enrollment in the study.

          -  Use of weight loss drugs within 3 months of date of randomization.

          -  Use of any oral anti-diabetic medication. (including metformin, sulphonylureas,
             thiazolidinediones, GLP-1 agonist, DDPIV inhibitors).

          -  Use of anti-depressants (SSRI, tricyclic, bupropion etc) within 3 months of screening.

          -  Use of diuretics (other than stable dosing of HCTZ), systemic corticosteroids (inhaled
             and intranasal corticosteroids are permitted), or any other medication within 3 weeks
             prior to any scheduled dose of study medication that may result in electrolyte
             depletion.

          -  Use of warfarin, digoxin, oral anti-coagulants (other than aspirin and non-steroidal
             anti-inflammatory drugs), or antiretroviral medications.

          -  Use of macrolide antibiotics during the interventional part of the study.

          -  Use of any investigational drug or device during the study or in the 30 days prior to
             first dosing with study medication.

          -  History or presence of allergy or hypersensitivity to sibutramine or any of its
             components, or drugs of this class, or a history of drug or other allergy that, in the
             opinion of the primary investigator, contraindicates study participation.

          -  Has donated 500 or more milliliters of blood within 56 days prior to dosing or has the
             intention of donating blood the month after completing the study.

          -  Is unwilling to adhere to protocol-stated restrictions while participating in the
             study.

          -  The Investigator considers the subject unfit for the study as a result of the medical
             interview, physical examination, or screening investigations.