Effects of Aprepitant on Satiation, Gastric Volume, Gastric Accommodation and Gastric Emptying

A Single-Center, Placebo-Controlled, Double-Blind Study to Evaluate the Effects of Aprepitant on Satiation, Gastric Volume, Gastric Accommodation and Gastric Emptying in Healthy Volunteers

This research study is being done to compare the effects of Aprepitant and placebo on fasting gastric volume, accommodation volume, satiation (fullness) and gastric emptying.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Aprepitant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Able to provide written consent
2. No medical problems or chronic diseases, specifically, no type 2 diabetes mellitus
3. Body Mass Index of 18-35 kg/m^2
4. Female subjects must have negative urine pregnancy tests and must not be lactating prior to receiving study medication and radiation exposure
5. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study
6. Female subjects unable to bear children must have this documented in the medical record (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period])

Exclusion criteria:

1. Diagnosis of gastrointestinal diseases
2. Structural or metabolic diseases that affect the gastrointestinal system

3. Unable to avoid the following over-the-counter medications 48 hours prior to the baseline period and throughout the study:

   • Medications that alter GI transit including laxatives, magnesium and aluminum containing antacids, prokinetics, erythromycin
   • Analgesic drugs including NSAIDs and cyclooxygenase-2 (COX-2) inhibitor. (NOTE: Stable doses of thyroid replacement, estrogen replacement, low-dose aspirin for cardioprotection, and birth control (but with adequate backup contraception as drug-interactions with birth control have not been conducted) are permissible.)
4. History of recent surgery (within 60 days of screening).
5. Acute or chronic illness or history of illness, which in the opinion of the investigator could pose a threat or harm to the subject or obscure interpretation of laboratory test results or interpretation of study data such as frequent angina, Class III or IV congestive heart failure, moderate impairment of renal or hepatic function, poorly controlled diabetes, etc.
6. Any clinically significant abnormalities on physical examination or laboratory abnormalities identified in the medical record, as determined by the investigator.
7. Acute GI illness within 48 hours of initiation of the baseline period.
8. Females who are pregnant or breastfeeding.
9. History of excessive alcohol use or substance abuse.
10. Participation in an investigational study within the 30 days prior to dosing in the present study.
11. Any other reason, which in the opinion of the investigator would confound proper interpretation of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aprepitant; Subjects will receive one tablet daily for 5 consecutive days. On Day 1 subjects will take a 125mg tablet, on Days 2-5, subjects will take an 80 mg tablet.	Drug: Aprepitant; Subjects will receive one tablet daily for 5 consecutive days. On Day 1 subjects will take a 125mg tablet, on Days 2-5, subjects will take an 80 mg tablet.; Other Names: Emend
Placebo Comparator: Placebo; Subjects will receive one placebo tablet daily for 5 consecutive days.	Drug: Placebo; Subjects will receive one placebo tablet daily for 5 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric Emptying Half-Time of Solids as Measured by Scintigraphy	The time for half of the ingested solids to leave the stomach.	Day 3, approximately 2 hours after radiolabeled meal is ingested
Satiation Expressed as Volume to Fullness	Subjects will do a satiation/nutrient drink test, consuming Ensure at a relatively constant rate of 30 ml/min. Subjects will record 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 reaches level 3.	Day 4, approximately 30 minutes after liquid meal
Fasting Gastric Volume as Measured by Single Photon Emission Computed Tomography (SPECT)	Subjects will arrive to the Clinical Research and Trials Unit (CRTU) fasting. A radioactive marker will be administered intravenously. After a 10-15 minute wait period a fasting scan will be acquired using a dual-head gamma camera.	Day 5, approximately 15 minutes after radioactive marker is administered
Postprandial Gastric Volume as Measured by SPECT	At the completion of the fasting scan, the subject will consume 300 ml of Ensure followed by a postprandial scan using a dual-head gamma camera.	Day 5, approximately 30 minutes after liquid meal
Accommodation Volume as Measured by SPECT	This variable is calculated as postprandial gastric volume minus fasting volume.	Day 5, approximately 30 minutes after liquid meal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solid Gastric Emptying: Proportion of Meal Emptied at 2 Hours	On Day 3, subjects will take part in a gastric emptying by scintigraphy test. Subjects will be given a scrambled egg breakfast with toast and a glass of milk. The eggs and milk contain a small amount of radioactive substance. At the completion of the meal, subjects will stand 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.	Day 3, approximately 2 hours after radiolabeled meal is ingested
Solid Gastric Emptying: Proportion of Meal Emptied at 4 Hours	On Day 3, subjects will take part in a gastric emptying by scintigraphy test. Subjects will be given a scrambled egg breakfast with toast and a glass of milk. The eggs and milk contain a small amount of radioactive substance. At the completion of the meal, subjects will stand 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 4 hours.	Day 3, approximately 4 hours after radiolabeled meal is ingested
Maximum Tolerated Volume on Satiation Test	On Day 4, subjects will do a satiation/nutrient drink test. Participants will record 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 reaches level 5.	Day 4, approximately 30 minutes after liquid meal
Individual Symptom Scores (Nausea, Bloating, Fullness, Pain) on Satiation Test	Postprandial symptoms of nausea, bloating, fullness, and pain will be measured using 100 mm horizontal visual analog scales, with the words "none" and "worst ever" anchored at each end.	Day 4, approximately 30 minutes after liquid meal
Aggregate Symptoms Score	Postprandial symptoms of nausea, bloating, fullness, and pain will be measured using 100 mm horizontal visual analog scales, with the words "none" and "worst ever" anchored at each end. The aggregate symptoms score is calculated by adding the mean individual scores. The lowest possible score would be 0 (none) and the highest maximum score possible is 400 (worst ever).	Day 4, approximately 1 hour after liquid meal
Gastric Volume Ratio	Postprandial/fasting gastric volume	Day 5, approximately 1 hour after radioactive marker is administered
Absolute postprandial gastric volume	This is the total postprandial gastric volume	Day 5, approximately 1 hour after radioactive marker is administered

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael Camilleri, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2017
• Primary Completion (Actual): November 20, 2017
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: December 7, 2016
• First Submitted That Met QC Criteria: December 9, 2016
• First Posted (Estimate): December 12, 2016

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: December 10, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant
• Other Study ID Numbers: 16-007929

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No