Pexacerfont for Stress-induced Food Craving

- INCLUSION CRITERIA:

1. Body Mass Index (BMI) > 22 kg/m(2)

2. Score of 15 or higher on the Dietary Restraint Scale, with endorsement of the Restraint

Scale item Do you give too much time and thought to food?

3. Age 21 - 65 years.

(4a) For women of childbearing potential: must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study drug, and agree to use an adequate method of contraception to avoid pregnancy for a period of 6 months beginning from first dose of randomized treatment. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Adequate methods of contraception for sexually active women are having a male sexual partner(s) who is surgically sterilized prior to inclusion; having a sexual partner(s) who is/are exclusively female; using oral contraceptives (either combined or progesterone only) with a single-barrier method of contraception consisting of spermicide and condom or diaphragm; using double-barrier contraception, specifically, a condom plus spermicide and a female diaphragm or cervical cap; or using an approved intrauterine device (IUD) with established efficacy.

(4b) Men, unless surgically sterilized (vasectomy with documentation of azoospermia), must agree to practice abstinence or use barrier contraception, and not donate sperm, for a period of 6 months beginning from first dose of randomized treatment.

EXCLUSION CRITERIA:

1. Current employment at NIDA IRP or Bristol-Myers Squibb (BMS), or being in the immediate family of an employee. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

2. Current participation in another clinical study that includes exposure to an investigational or non-investigational drug or device.

3. Participation in a clinical study for a condition related to weight or dieting within the preceding month.

4. Any history of participation in a trial involving pexacerfont or closely related compounds.

5. Any medical condition or laboratory finding that, in the judgment of the investigators, could adversely affect safety or study integrity. Examples include but are not limited to diabetes type 1 and type 2, ischemic heart disease, uncontrolled hypertension, and history of cerebrovascular accident or transient ischemic attack.

6. For women: pregnancy, breastfeeding, or planning to become pregnant within 6 months from the administration of first dose of study drug.

7. Past or present diagnosis of any eating disorder, including Anorexia Nervosa, Bulimia Nervosa, and Eating Disorder NOS (e.g., Binge-Eating Disorder). (Eating-disordered individuals probably represent a distinct population and should therefore be studied separately.)

8. Past or present diagnosis of schizophrenia, bipolar disease, or any psychotic disorder; past or present diagnosis of dementia or any other disorder that has led to a clinically significant cognitive impairment; present diagnosis of any mood or anxiety disorder; any other psychiatric condition that presently requires, or in the past month has required, pharmacological intervention.

9. Past or present diagnosis of any substance-use disorder except nicotine dependence.

10. Urine tests positive for illegal drugs.

11. Evidence of thyroid disorder by medical history or screening physical exam, with TSH < 0.36 or greater than 3.74 UIU/ml; or current or history of use of thyroid medication.

12. Adrenal or pituitary pathology as evidenced by medical history or suggested by abnormal screening labs.

13. Current seizure disorder or a significant history (as judged by the investigators) of a seizure disorder, other significant neurological disorders (e.g., Parkinson's Disease, multiple sclerosis, stroke, neurodegenerative disease, cerebral palsy) or severe head trauma (including closed head trauma, penetrating head injury, skull fracture, or intracranial hemorrhage), or CNS tumor.

14. Active liver disease or a history of hepatic intolerance to medications that, in the investigators' judgment, is medically significant.

15. History of diabetes mellitus type I and II or gastric bypass or reduction surgery.

Justification: illnesses that change metabolism or the absorption from the GI tract, would interfere with drug metabolism or absorption).

16. Difficulty swallowing tablets or capsules.

17. Exclusionary physical and laboratory test findings:

QTc > 475 msec

platelets less than or equal to 75,000/mm(3)

hemoglobin less than or equal to 9g/dL

neutrophils, absolute less than or equal to 1000/mm3

SGOT (AST) > 2.5 times upper limit of normal

SGPT (ALT) > 2.5 times upper limit of normal

bilirubin 2 times upper limit of normal

GFR < 60mL/min/1.73m2 or significant proteinuria

diastolic blood pressure > 105 mmHg

TSH < 0.36 or > 3.74 UIU/ml

18. Current use or history of use in the last 3 months of psychiatric medications, including but not limited to antidepressants, lithium, antipsychotics, anxiolytics, antiepileptics, opiates, or hypnotics.

19. Any change in a non-excluded medication in the past 3 months.

20. Systemic intake of corticosteroids acutely within 2 weeks or chronically (> 28 days) within the last 6 months. (Topical hydrocortisone and inhaled corticosteroids are allowed.)

21. Use of medications that are CYP3A4 inhibitors or inducers (see Appendix 3); study applicants should not take these medications for at least 7 days prior to randomization and during the remainder of the study.

22. Dietary restrictions or food aversions that would interfere with valid assessment of eating in our laboratory sessions.