Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients

NCT01834404 | Completed Phase 4 Results

• 3 other identifiers: 13-000948R01DK067071UL1TR000135
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Obesity

Keywords

Obesity; BMI; Incretin; Satiety; Phentermine; Topiramate

Outcome Measures

Primary Outcomes (6)

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

  Gastric emptying of solids half-time is defined as the time for half of the ingested solids to leave the stomach. 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.

  Day 15, approximately 2 hours after radiolabeled meal was ingested

• Fasting Gastric Volume

  Fasting whole gastric volume was measured by Technetium (99mTc)-SPECT Imaging. Subjects reported to the clinic after an overnight fast. 99mTC was given by an intravenous injection in the forearm. Tomographic images of the gastric wall were obtained throughout the long axis of the stomach using a dual-head gamma camera that rotates around the body. This allows assessment of the radiolabeled circumference of the gastric wall, rather than the intragastric content.

  Day 13, approximately 10 minutes after Technetium (99mTC) injection

• Postprandial Gastric Volume

  Postprandial gastric volume was measured by 99mTc-SPECT Imaging. Subjects reported to the clinic after an overnight fast. 99mTC was given by an intravenous injection in the forearm. After the liquid meal tomographic images of the gastric wall were obtained throughout the long axis of the stomach using a dual-head gamma camera that rotates around the body. This allows assessment of the radiolabeled circumference of the gastric wall, rather than the intragastric content.

  Day 13, approximately 30 minutes after liquid meal

• Volume to Fullness

  At visit 5, subjects did a satiation/nutrient drink test. Participants recorded their sensations every 5 minutes using a numerical scale from 0-5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation). This measure was the volume consumed when the fullness sensation reached level 3.

  Day 14, approximately 30 minutes after liquid meal

• Maximum Tolerated Volume

  At visit 5, subjects did a satiation/nutrient drink test. Participants recorded their sensations every 5 minutes using a numerical scale from 0-5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation). This measure is the volume consumed when the fullness sensation reached level 5.

  Day 14, approximately 30 minutes after liquid meal

• Buffet Meal Intake

  At visit 4 subjects underwent imaging to measure the volume of their stomach, fasting and after ingesting a liquid nutrient drink. Four hours after the liquid meal, subjects were invited to eat, over a 30-minute period, a standard "all you can eat" meal vegetable lasagna, vanilla pudding, and skim milk. The total Kcal of the food consumed was analyzed by using validated software.

  Day 13, approximately 4.5 hours after liquid meal

Secondary Outcomes (7)

• Solid Gastric Emptying: Proportion of Meal Emptied at 2 Hours

  Day 15, approximately 2 hours after radiolabeled meal was ingested

• Solid Gastric Emptying: Proportion Remaining at 4 Hours

  Day 15, approximately 4 hours after radiolabeled meal was ingested

• Change in Postprandial Gastric Volume

  Day 13, approximately approximately 30 min after liquid meal

• Fasting Ghrelin

  Day 14, before liquid meal

• Peak Postprandial Level of Cholecystokinin (CCK)

  Day 14, approximately 45 minutes after liquid meal

Study Arms (2)

Phentermine-Topiramate ER

EXPERIMENTAL

Qualifying participants were assigned to the Phentermine-Topiramate ER for a minimum of 5 days. The dosing of the study drug was phentermine 3.75 mg / topiramate 23 mg days 1-5. The dosing of the study drug was increased to phentermine 7.5 mg / topiramate 46 mg days 6-14.

Drug: Phentermine-Topiramate ER

Placebo

PLACEBO COMPARATOR

Qualifying participants were assigned to placebo for a minimum of 5 days. Placebo pills matched the study drug in appearance for the 2 dose levels.

Drug: Placebo

Interventions

Phentermine-Topiramate ER DRUG

The dosing of the study drug was phentermine 3.75 mg / topiramate 23 mg days 1-5. The dosing of the study drug was increased to phentermine 7.5 mg / topiramate 46 mg days 6-14.

Also known as: Qsymia

Phentermine-Topiramate ER

Placebo DRUG

Placebo pills matched the study drug in appearance for the 2 dose levels.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Acosta A, Camilleri M, Shin A, Vazquez-Roque MI, Iturrino J, Burton D, O'Neill J, Eckert D, Zinsmeister AR. Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy. Gastroenterology. 2015 Mar;148(3):537-546.e4. doi: 10.1053/j.gastro.2014.11.020. Epub 2014 Dec 6.

  PMID: 25486131 RESULT

MeSH Terms

Conditions

Obesity

Interventions

Qsymia

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Michael Camilleri
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-284-6218

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: March 27, 2013
• First Posted: April 17, 2013
• Study Start: April 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: February 23, 2015
• Results First Posted: February 23, 2015

Record last verified: 2015-02

Locations

US (1)