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GM-611, a motilin-receptor agonist, accelerates gastric emptying in patients with symptomatic gastroparesis (GP)
was 0.0982 (99.9274 % accuracy). Conclusions. OABTis an accuratetest for gastric emptying measurement.
GM-611 20 mg BID 20 mg TID
Placebo
10 mg BID
30 mg BID
21 -16.10
16 -70.42
19 -67.56
18 -55.82
20 -74.57*
10 -9.92
16 -70.42*
18 -66.90
17 -53.30
20 -74.57*
11 -17.73
10 -64.15
11 -91.70"
10 -69.22*
11 -6626
8 0.84
6 -80.89
7 -27.91
7 -30.55
9 -84.73
Intent-to-treat
2374
N Mean% Change
Early Gastric Emptying Results In Absorption Of Nutrients In Healthy Humans Melvin Samsom, Univ Medical Ctr, Utrecht Netherlands; Trygve Hausken, HaukelandHosp, Bergen Norway; Willem Renooij, Univ Medical Ctr, Utrecht Netherlands
Evalueble
Background: Recently several techniques have been developed to study gastric emptying directly or indirectly. The 13C-octanoic-acidbreathtest is an indirect method to measure gastric emptying using a fast metabolizedtriglyceride enriched with ~3C.In contrast, Doppler ultrasonography is a direct method to measure real time transpyloric flow. Aim of the study was to investigate whether back and fro movement at the level of the pylorus detected by Doppler ultrasonographyso called duodenal tasting results in absorption of nutrients. In 8 healthy volunteers (5 males, mean age 26 (4) yr, weight 81 (SD 17) kg) transpyloric flow was measured using Doppler ultrasonography (VingMed, Norway). 100 mg ~3C enriched octanoic acid was added to a liquid nutrient meal (75 g dextrose in 500 ml) which was ingested within 2.5 min. Before and at 2.5, 5.0, 7.5 and 10 min after the start of meal ingestion breathsampleswere collectedand analysedusingan isotope ratio mass spectrometer (Breathmat, Finnegan, Bremen). At the same time intervals blood samples were drawn to measure blood glucose concentrations.Transpyloric flow was measuredfrom time zero (start of ingestion) to 10 min after the start of ingestion of the meal. Timing, duration, direction, emptying index (n x mean duration) and reflux index (n x duration) were calculated. Results: first emptying episode was observed 50.3 (15.5) sec and first peristalted related flow 132.5 (17.5) sec after the start of ingestion. Emptying index (El) and reflux index (RI) during the first 2.5 rain period were significantly higher than in fourth period [El: 22.3 (8.0) vs 2.1 (1.1), p
N Mean % Change EvaluableDiabetic N Mean % Change Evaluableidiopathic N Mean% Change
* Significanceat p
2375 GM-611, a Motilin-Receptor Agonist, Accelerates Gastric Emptying in Patients with Symptomatic Gastroparesis (Gr). John Fang, Salt Lake City VA Medical Centers, Salt Lake City, UT; Richard McCallum, Div of Gastroenterology,Univ of Kansas Medical Ctr, KansasCity, KS; Mark K. Kipnes, Diabetes and Glandular Disease Clin, PA, San Antonio, TX; GervaisTougas, McMaster Univ Medical Ctr, Hamilton Canada;Philip B. Miner Jr, OklahomaFdn for Digest Research, Oklahoma City, OK; John K. Dibaise, Univ of Nebraska Medical Ctr, Omaha, NB; Colleen M. Schmitt, Southeastern Clin Research,Chattanooga,TN; Thomas L. Abelf, Univ of Tennessee, Memphis, TN; Cynthia Clinkingbeard, Robert Hardi, Metropolitan Gastroenterology Group, Chevy Chase, MD; G Nicholas Verne, GastroenterologyDept 111C, VA Medical Ctr, Gainesville,FL; Daniel Pertschuk, Chugai Biopharmaceuticals,Inc, San Diego, CA Aim: By definition, patients with GP have delayed gastric emptying (GE). This randomized, double-blind, placebo controlled study examinedthe effects of 4 doses of GM-611 on solid GE in patients with symptomatic GP, defined as gastric retention >6 % at 4 hours using a validatedscintigraphic method (Tougaset al, AJG 2000;95:1456-62). Methods: 104 GP patients received either 1 of 4 dosing regimens (10 mg BID, 20 mg BID, 20 mg TID, 30 mg BID) or placebo. Randomizationwas stratified by etiology: idiopathic vs. diabeticGP. GEwas measured at baseline and after 28 days of treatment. The improvement from baselineto Day 28 was analyzed(SeeTable). Results: Overall,the most statistically significant improvementin gastric emptying was observed in the 30 mg BID (p=O.01) and the 10 mg BID doses (p=O.04) in evaluablepatients.All doses of GM-611 showeda statistically significant mean percentchange from baselinecompared with placebowhen adjusted for baselinedifferences. Therefore, GM611 showed potent prokinetic activity in patients with symptomatic GP. Conclusion: Further controlled clinical trials are warranted to establish the role of this agent in patients with symptomatic GP.
Effect of baclofenon gas~icemptyingtl/2 (rain) mealtype
saline
lmg/kg baclofen
2mglkgbaclofen
non.nutrientliquid nutrient liquid solid
15 (1) 26 (3) 150 (12)
11 (1) 28 (2) 01 (14)+
22 (4)* 35 (2) 59 (6)++**
+significantlydifferentto saline(+p
A-467
GM-611 20 mg BID 20 mg TID
Placebo
10 mg BID
30 mg BID
21 -16.10
16 -70.42
19 -67.56
18 -55.82
20 -74.57*
10 -9.92
16 -70.42*
18 -66.90
17 -53.30
20 -74.57*
11 -17.73
10 -64.15
11 -91.70"
10 -69.22*
11 -6626
8 0.84
6 -80.89
7 -27.91
7 -30.55
9 -84.73
Intent-to-treat
2374
N Mean% Change
Early Gastric Emptying Results In Absorption Of Nutrients In Healthy Humans Melvin Samsom, Univ Medical Ctr, Utrecht Netherlands; Trygve Hausken, HaukelandHosp, Bergen Norway; Willem Renooij, Univ Medical Ctr, Utrecht Netherlands
Evalueble
Background: Recently several techniques have been developed to study gastric emptying directly or indirectly. The 13C-octanoic-acidbreathtest is an indirect method to measure gastric emptying using a fast metabolizedtriglyceride enriched with ~3C.In contrast, Doppler ultrasonography is a direct method to measure real time transpyloric flow. Aim of the study was to investigate whether back and fro movement at the level of the pylorus detected by Doppler ultrasonographyso called duodenal tasting results in absorption of nutrients. In 8 healthy volunteers (5 males, mean age 26 (4) yr, weight 81 (SD 17) kg) transpyloric flow was measured using Doppler ultrasonography (VingMed, Norway). 100 mg ~3C enriched octanoic acid was added to a liquid nutrient meal (75 g dextrose in 500 ml) which was ingested within 2.5 min. Before and at 2.5, 5.0, 7.5 and 10 min after the start of meal ingestion breathsampleswere collectedand analysedusingan isotope ratio mass spectrometer (Breathmat, Finnegan, Bremen). At the same time intervals blood samples were drawn to measure blood glucose concentrations.Transpyloric flow was measuredfrom time zero (start of ingestion) to 10 min after the start of ingestion of the meal. Timing, duration, direction, emptying index (n x mean duration) and reflux index (n x duration) were calculated. Results: first emptying episode was observed 50.3 (15.5) sec and first peristalted related flow 132.5 (17.5) sec after the start of ingestion. Emptying index (El) and reflux index (RI) during the first 2.5 rain period were significantly higher than in fourth period [El: 22.3 (8.0) vs 2.1 (1.1), p
N Mean % Change EvaluableDiabetic N Mean % Change Evaluableidiopathic N Mean% Change
* Significanceat p
2375 GM-611, a Motilin-Receptor Agonist, Accelerates Gastric Emptying in Patients with Symptomatic Gastroparesis (Gr). John Fang, Salt Lake City VA Medical Centers, Salt Lake City, UT; Richard McCallum, Div of Gastroenterology,Univ of Kansas Medical Ctr, KansasCity, KS; Mark K. Kipnes, Diabetes and Glandular Disease Clin, PA, San Antonio, TX; GervaisTougas, McMaster Univ Medical Ctr, Hamilton Canada;Philip B. Miner Jr, OklahomaFdn for Digest Research, Oklahoma City, OK; John K. Dibaise, Univ of Nebraska Medical Ctr, Omaha, NB; Colleen M. Schmitt, Southeastern Clin Research,Chattanooga,TN; Thomas L. Abelf, Univ of Tennessee, Memphis, TN; Cynthia Clinkingbeard, Robert Hardi, Metropolitan Gastroenterology Group, Chevy Chase, MD; G Nicholas Verne, GastroenterologyDept 111C, VA Medical Ctr, Gainesville,FL; Daniel Pertschuk, Chugai Biopharmaceuticals,Inc, San Diego, CA Aim: By definition, patients with GP have delayed gastric emptying (GE). This randomized, double-blind, placebo controlled study examinedthe effects of 4 doses of GM-611 on solid GE in patients with symptomatic GP, defined as gastric retention >6 % at 4 hours using a validatedscintigraphic method (Tougaset al, AJG 2000;95:1456-62). Methods: 104 GP patients received either 1 of 4 dosing regimens (10 mg BID, 20 mg BID, 20 mg TID, 30 mg BID) or placebo. Randomizationwas stratified by etiology: idiopathic vs. diabeticGP. GEwas measured at baseline and after 28 days of treatment. The improvement from baselineto Day 28 was analyzed(SeeTable). Results: Overall,the most statistically significant improvementin gastric emptying was observed in the 30 mg BID (p=O.01) and the 10 mg BID doses (p=O.04) in evaluablepatients.All doses of GM-611 showeda statistically significant mean percentchange from baselinecompared with placebowhen adjusted for baselinedifferences. Therefore, GM611 showed potent prokinetic activity in patients with symptomatic GP. Conclusion: Further controlled clinical trials are warranted to establish the role of this agent in patients with symptomatic GP.
Effect of baclofenon gas~icemptyingtl/2 (rain) mealtype
saline
lmg/kg baclofen
2mglkgbaclofen
non.nutrientliquid nutrient liquid solid
15 (1) 26 (3) 150 (12)
11 (1) 28 (2) 01 (14)+
22 (4)* 35 (2) 59 (6)++**
+significantlydifferentto saline(+p
A-467