Trial Outcomes & Findings for Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients (NCT NCT01834404)
NCT ID: NCT01834404
Last Updated: 2015-02-23
Results Overview
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.
COMPLETED
PHASE4
24 participants
Day 15, approximately 2 hours after radiolabeled meal was ingested
2015-02-23
Participant Flow
Subjects were recruited from patients attending the Mayo Clinic in Rochester, Minnesota.
Participant milestones
| Measure |
Phentermine-Topiramate ER
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.
|
Placebo
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.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
|
Overall Study
COMPLETED
|
12
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients
Baseline characteristics by cohort
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.8 years
STANDARD_DEVIATION 1.8 • n=99 Participants
|
38.2 years
STANDARD_DEVIATION 2.4 • n=107 Participants
|
34.8 years
STANDARD_DEVIATION 7.4 • n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=99 Participants
|
12 participants
n=107 Participants
|
24 participants
n=206 Participants
|
|
Body Mass Index (BMI)
|
35.8 kg/m^2
STANDARD_DEVIATION 0.9 • n=99 Participants
|
33.9 kg/m^2
STANDARD_DEVIATION 1.9 • n=107 Participants
|
34.9 kg/m^2
STANDARD_DEVIATION 5.1 • n=206 Participants
|
|
Waist Circumference
|
108.5 cm
STANDARD_DEVIATION 2.2 • n=99 Participants
|
111.2 cm
STANDARD_DEVIATION 2.2 • n=107 Participants
|
109.8 cm
STANDARD_DEVIATION 7.5 • n=206 Participants
|
|
Fasting Plasma Glucose
|
94.2 mg/dL
STANDARD_DEVIATION 2.7 • n=99 Participants
|
96.5 mg/dL
STANDARD_DEVIATION 3.6 • n=107 Participants
|
95.3 mg/dL
STANDARD_DEVIATION 10.6 • n=206 Participants
|
|
Baseline Volume to Fullness
|
712 ml
STANDARD_DEVIATION 86 • n=99 Participants
|
710 ml
STANDARD_DEVIATION 95 • n=107 Participants
|
711.3 ml
STANDARD_DEVIATION 306.3 • n=206 Participants
|
|
Baseline Maximum Tolerated Volume
|
1368 ml
STANDARD_DEVIATION 111 • n=99 Participants
|
1227 ml
STANDARD_DEVIATION 111 • n=107 Participants
|
1297.8 ml
STANDARD_DEVIATION 383.2 • n=206 Participants
|
PRIMARY outcome
Timeframe: Day 15, approximately 2 hours after radiolabeled meal was ingestedGastric 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.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Gastric Emptying of Solids Half-Time (T 1/2)
|
109 minutes
Standard Error 7
|
88 minutes
Standard Error 7
|
PRIMARY outcome
Timeframe: Day 13, approximately 10 minutes after Technetium (99mTC) injectionFasting 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.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Fasting Gastric Volume
|
227 mL
Standard Error 25
|
261 mL
Standard Error 25
|
PRIMARY outcome
Timeframe: Day 13, approximately 30 minutes after liquid mealPostprandial 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.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Postprandial Gastric Volume
|
680 mL
Standard Error 37
|
681 mL
Standard Error 37
|
PRIMARY outcome
Timeframe: Day 14, approximately 30 minutes after liquid mealAt 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.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Volume to Fullness
|
570 mL
Standard Error 63.2
|
630 mL
Standard Error 61.1
|
PRIMARY outcome
Timeframe: Day 14, approximately 30 minutes after liquid mealAt 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.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Maximum Tolerated Volume
|
966 mL
Standard Error 79
|
1108 mL
Standard Error 79
|
PRIMARY outcome
Timeframe: Day 13, approximately 4.5 hours after liquid mealAt 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.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Buffet Meal Intake
|
728 Kcal
Standard Error 79
|
988 Kcal
Standard Error 79
|
SECONDARY outcome
Timeframe: Day 15, approximately 2 hours after radiolabeled meal was ingestedAt 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. This outcome measure is the proportion of the radiolabeled meal emptied at 2 hours.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Solid Gastric Emptying: Proportion of Meal Emptied at 2 Hours
|
0.56 proportion of meal emptied
Standard Error 0.03
|
0.66 proportion of meal emptied
Standard Error 0.03
|
SECONDARY outcome
Timeframe: Day 15, approximately 4 hours after radiolabeled meal was ingestedAt 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. This outcome measure is the proportion of the radiolabeled meal remaining at 4 hours.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Solid Gastric Emptying: Proportion Remaining at 4 Hours
|
0.09 proportion of meal remaining
Standard Error 0.02
|
0.16 proportion of meal remaining
Standard Error 0.02
|
SECONDARY outcome
Timeframe: Day 13, approximately approximately 30 min after liquid mealChange between postprandial and fasting whole gastric volume by 99mTc-SPECT Imaging. A noninvasive SPECT method was used to measure gastric volume during fasting and 32 min after a liquid nutritional supplement meal. Subjects reported to the clinic after an overnight fast. 99mTC was given by an intravenous injection in the forearm. The first fasting scan was obtained, and the study medication was given s.c. After 10 min, a 2nd fasting post medication scan was obtained, and the meal consumed; then two serial postprandial scans were obtained. Each scan required 9-12 min. 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.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Change in Postprandial Gastric Volume
|
453 mL
Standard Error 24
|
420 mL
Standard Error 24
|
SECONDARY outcome
Timeframe: Day 14, before liquid mealPlasma gastrointestinal hormone total ghrelin was measured by radioimmunoassay.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Fasting Ghrelin
|
78.1 pg/mL
Standard Error 5.6
|
82.6 pg/mL
Standard Error 10.8
|
SECONDARY outcome
Timeframe: Day 14, approximately 45 minutes after liquid mealPlasma gastrointestinal hormone CCK was measured by radioimmunoassay based on an antibody with very low cross-reactivity to gastrin 17 and its sulfated counterpart, and to sensitivity to a concentration of 0.3 pmol/L.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Peak Postprandial Level of Cholecystokinin (CCK)
|
8.1 pg/mL
Standard Error 0.9
|
8.3 pg/mL
Standard Error 1
|
SECONDARY outcome
Timeframe: Day 14, approximately 45 minutes after liquid mealPlasma gastrointestinal hormone GLP-1 was measured by radioimmunoassay.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Peak Postprandial Level of Total Glucagon-Like Peptide-1 (GLP-1)
|
13.0 pg/mL
Standard Error 1.8
|
11.9 pg/mL
Standard Error 1.6
|
SECONDARY outcome
Timeframe: Day 14, approximately 45 minutes after liquid mealPlasma gastrointestinal hormone PYY was measured by radioimmunoassay.
Outcome measures
| Measure |
Phentermine-Topiramate ER
n=12 Participants
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.
|
Placebo
n=12 Participants
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.
|
|---|---|---|
|
Peak Postprandial Level of Total Peptide Tyrosine-Tyrosine (PYY)
|
195.3 pg/mL
Standard Error 21.2
|
166 pg/mL
Standard Error 15.7
|
Adverse Events
Phentermine-Topiramate ER
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place