Effect of a CCK-1R Agonist on Food Intake in Humans (GSK)

St. Luke's-Roosevelt Hospital Center

Status and phase: Terminated; Phase 2

Conditions: Bulimia

Treatments: Drug: Placebo; Behavioral: Instructions to eat normally; Behavioral: Instructions to binge eat; Drug: GSKI181771X (CCK-1R agonist)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00600743

07-101

Details and patient eligibility

About

The ultimate aim of this study is to test the hypothesis that the oral cholecystokinin (CCK) agonist GSKI181771X will reduce the size of a binge meal among individuals with Bulimia Nervosa. The study will be conducted in phases. First, an effective dose for reducing food intake, when normal subjects eat normally will be attained. Next, it will be determined whether intake at this dose is reduced in control subjects instructed to eat to capacity. If the dose is still effective compared to placebo, the same dose will be tested in patients with bulimia nervosa.

Full description

This study tests the hypothesis that an oral CCK antagonist GSKI181771X will reduce the size of a binge meal. It was intended to study the effects of increasing doses on antagonist on normal individuals to find an effective dose in a non-binge meal before moving to a binge meal. Once the effects of the antagonist on a binge meal were found, the compound would be used on patients with bulimia nervosa. However, the product expired and more was not available before the patients were tested. Data are presented for the normal participants who were instructed to eat normally, followed by a group that was instructed to binge eat. Comparisons were made between groups with different instructions and between binge and normal meals.

Enrollment: 40 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Both controls and patients will be female, 18 to 45 years old, and within 80-120% of ideal body weight (Metropolitan Life Insurance, 1983). Inclusion and exclusion will be evaluated using the following guidelines:

Normal Controls:

• No current or past psychiatric illness
• No history of binge eating or vomiting
• 80-120% ideal weight
• Of non-childbearing potential (i.e. physiologically incapable of becoming pregnant or surgically sterile)
• If of childbearing potential, willing to use an acceptable method of birth-control (please see list in "Exclusion" section)

Patients with Bulimia Nervosa:

• DSM-IV (diagnostic statistical manual - American Psychiatric Association) criteria for bulimia nervosa
• Duration of illness > 1 year
• Purging after binges via self-induced vomiting

(Same as controls for remaining inclusion criteria)

Exclusion criteria

Normal Controls:

• Significant medical illness: CBC, Chem-1, serum electrolytes (sodium, potassium, chloride, CO2), glucose, BUN (blood urea nitrogen), creatinine, Alk Phos, ALT (SGPT), AST (SGOT), LDH, total bilirubin, total protein, albumin, globulin, A/G ratio, calcium, phosphorus, uric acid, cholesterol, triglyceride

• ALT outside of upper limit of normal: Chem-1

• History of gallstones, pancreatitis or cholecystitis

• Current medication

• Hypersensitivity to benzodiazepines (contraindication in DCSI v02, 1-March-2006)

• Drug or alcohol abuse in last 3 mts

• Pregnancy

• Unable or unwilling to use highly effective methods of contraception for the duration of the study until an insignificant amount of the investigational product remains in the subject (i.e. at least 5 terminal phase half-lives). Examples of highly effective methods of contraception are:

  • Implants of levonorgestrel, or
  • Injectable progestogen, or
  • Oral birth control pills for at least 3 monthly cycles prior to administration of study drug + continuation for 24 hrs after last dose of study drug, or
  • Double-barrier method (e.g. condom, diaphragm) with spermicide

Note-Significant medical illness is any illness requiring continued care, i.e. chronic medication. Examples include hypertension, diabetes, and systemic lupus erythematosis. Subjects with seasonal allergies or occasional urinary tract infections will be included.

Patients with Bulimia Nervosa:

• Same as controls

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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40 participants in 8 patient groups, including a placebo group

1 'Instructions to eat normally'

Placebo Comparator group

Description:

'Instructions to eat normally' Placebo 1 mg dose

Treatment:

Drug: Placebo

Behavioral: Instructions to eat normally

2 'Instructions to eat normally'

Active Comparator group

Description:

'Instructions to eat normally' drug 1 mg dose 'GSKI181771X (CCK-1R agonist)'

Treatment:

Drug: GSKI181771X (CCK-1R agonist)

Behavioral: Instructions to eat normally

3 'Instructions to eat normally'

Placebo Comparator group

Description:

'Instructions to eat normally' 2 mg placebo

Treatment:

Drug: Placebo

Behavioral: Instructions to eat normally

4 'Instructions to eat normally'

Active Comparator group

Description:

'Instructions to eat normally' 2 mg drug 'GSKI181771X (CCK-1R agonist)'

Treatment:

Drug: GSKI181771X (CCK-1R agonist)

Behavioral: Instructions to eat normally

5 'Instructions to eat normally'

Placebo Comparator group

Description:

'Instructions to eat normally' 4 mg placebo

Treatment:

Drug: Placebo

Behavioral: Instructions to eat normally

6 'Instructions to eat normally'

Active Comparator group

Description:

'Instructions to eat normally' 4 mg drug 'GSKI181771X (CCK-1R agonist)'

Treatment:

Drug: GSKI181771X (CCK-1R agonist)

Behavioral: Instructions to eat normally

7 Instructions to binge eat

Placebo Comparator group

Description:

Instructions to binge eat 4 mg placebo

Treatment:

Drug: Placebo

Behavioral: Instructions to binge eat

8 Instructions to binge eat

Active Comparator group

Description:

Instructions to binge eat 4 mg drug 'GSKI181771X (CCK-1R agonist)'

Treatment:

Drug: GSKI181771X (CCK-1R agonist)

Behavioral: Instructions to binge eat