Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients

Condition(s) targeted: Obesity

Intervention: Phentermine-Topiramate ER (Drug); Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
Michael Camilleri, MD, Principal Investigator, Affiliation: Mayo Clinic

Our overall goal is to determine the effect of Phentermine and Topiramate ER on gastric emptying, gastric accommodation, satiety, and satiation in obese participants.

Official title: Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Gastric Emptying of Solids Half-Time (T 1/2)

Fasting Gastric Volume

Postprandial Gastric Volume

Volume to Fullness

Maximum Tolerated Volume

Buffet Meal Intake

Secondary outcome:

Solid Gastric Emptying: Proportion of Meal Emptied at 2 Hours

Solid Gastric Emptying: Proportion Remaining at 4 Hours

Change in Postprandial Gastric Volume

Fasting Ghrelin

Peak Postprandial Level of Cholecystokinin (CCK)

Peak Postprandial Level of Total Glucagon-Like Peptide-1 (GLP-1)

Peak Postprandial Level of Total Peptide Tyrosine-Tyrosine (PYY)

Detailed description: Investigators propose a randomized controlled trial of combination phentermine topiramate ER versus placebo given orally for 10-15 days. At visit 1 subjects had a brief interview, body measurements, and completed 4 questionnaires to rule out any gastrointestinal or significant psychological distress. At visit 2 subjects did a satiation/nutrient drink test. They drank a nutrient drink until they reached the maximum volume that could be tolerated, symptoms were recorded and blood samples taken at 4 times. They were randomized to one of the arms, and received a 5 day supply of study medication or placebo. The dosing of the study drug was phentermine 3. 75 mg / topiramate 23 mg days 1-5. At visit 3 subjects returned to pick up a nine day supply of study medication or placebo. The dosing of the study drug was increased to phentermine 7. 5 mg / topiramate 46 mg days 6-14. At visit 4 subjects underwent imaging to measure the volume of their stomach with an external camera that revolved around abdomen while they were lying on a table. Stomach volume was checked during fasting, starting 10 min after an intravenous injection of a radioactive material. The subjects ingested more of the liquid nutrient drink and 2 more images were obtained over 30 minutes. On the same day, subjects participated in an all you can eat meal, starting 4 hours after the ingestion of the liquid nutrient drink. At visit 5 subjects repeated the satiation/nutrient drink test. They drank a nutrient drink until they reached the maximum volume that could be tolerated, symptoms were recorded and blood samples taken at 4 times. At visit 6 subjects took part in a gastric emptying by scintigraphy test. Subjects were given a scrambled egg breakfast with toast and a glass of milk. The eggs and milk contained a small amount of radioactive substance. At the completion of the meal, subjects stood in front of a special camera and pictures were taken at specific intervals.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

INCLUSION CRITERIA:

- Obese subjects with BMI> 30 Kg/m^2. Otherwise healthy individuals who are not

currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, endocrine (other than hyperglycemia not requiring medical therapy) and unstable psychiatric disease.

- Women of childbearing potential will have negative pregnancy test before initiation

of medication. EXCLUSION CRITERIA:

- Weight >300 lbs, which is the limit of safety for the SPECT scanner

- Concomitant use of appetite suppressants (i. e., caffeine based or diethylpropion) or

orlistat (Xenical®)

- Uncontrolled hypertension (Blood pressure greater than 160/90 mmHg)

- Concentration of fasting glucose greater than 240 mg/dl

- Concentration of triglycerides greater than 400 mg/dl

- Type 1 Diabetes

- Use of anti-diabetic drugs other than metformin,

- History of nephrolithiasis,

- Recurrent major depression, presence or history of suicidal behavior or ideation with

intent to act, and current substantial depressive symptoms (Patient Health Questionnaire-9, 21 total score ≥10).

- Concomitant use of Monoamine Oxidase Inhibitors (MAOI) (i. e., phenelzine,

selegiline), serotonergic agents, and other centrally acting appetite suppressants

- Significant psychiatric dysfunction based upon screening with the Hospital Anxiety

and Depression Scale [HADS] self-administered alcoholism screening test (SAAST, substance abuse) and the questionnaire on eating and weight patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a Hospital Anxiety and Depression Scale (HADS) score ≥11 in any of the subscales or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up.

- End stage renal disease or liver cirrhosis

- Intake of medication that could interfere with the interpretation of the study or

cause drug interaction (i. e., ketoconazole, erythromycin). Specifically, birth control pill, estrogen replacement therapy, and thyroxine replacement are permissible.

Mayo Clinic in Rochester, Rochester, Minnesota 55905, United States

Starting date: April 2013
Last updated: February 10, 2015