Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02308254




Registration number
NCT02308254
Ethics application status
Date submitted
3/11/2014
Date registered
4/12/2014
Date last updated
29/10/2015

Titles & IDs
Public title
Drug Trial of Lixisenatide on Gastric Emptying and Blood Pressure Drops in Type 2 Diabetics and Healthy People
Scientific title
Effects of Lixisenatide on Gastric Emptying, Glycaemia and 'Postprandial' Blood Pressure in Type 2 Diabetes and Healthy Subjects.
Secondary ID [1] 0 0
130419
Universal Trial Number (UTN)
Trial acronym
Lixi
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus 0 0
Gastroparesis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lixisenatide
Treatment: Drugs - Placebo

Active Comparator: Lixisenatide - Lixisenatide: 10 mcg, one subcutaneous injection dose

Placebo Comparator: Placebo - Matching placebo: one subcutaneous injection dose


Treatment: Drugs: Lixisenatide
Abdominal administration

Treatment: Drugs: Placebo
Abdominal administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Blood Pressure
Timepoint [1] 0 0
4.5 hours per study
Secondary outcome [1] 0 0
Heart rate
Timepoint [1] 0 0
4.5 hours per study
Secondary outcome [2] 0 0
Gastric emptying rate
Timepoint [2] 0 0
3 hours per study
Secondary outcome [3] 0 0
Blood glucose concentration
Timepoint [3] 0 0
3 hours per study

Eligibility
Key inclusion criteria
- Healthy subjects:

- Male or female (females using appropriate contraceptive method or willing to
undergo pregnancy test)

- Body Mass Index (BMI) 19 - 30 kg/m2

- Type 2 Diabetic Patients:

- As per "healthy subjects"

- Type 2 diabetes (World Health Organisation (WHO) criteria) managed by diet alone
or on metformin

- Glycated haemoglobin >6.0% and <8.5%
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Subjects with a history of severe respiratory, cardiovascular, hepatic and/or renal
disease (severe in that the social or physical manifestations of the disease, or
living with the condition, impact negatively and significantly on the individuals'
ability to lead a normal day to day life), chronic alcohol abuse or epilepsy (excluded
by history) or if iron status, or liver function tests are outside the following
ranges:

1. Alanine aminotransferase (ALT) 0 - 55 U/L

2. Alkaline phosphatase 30 - 110 U/L

3. Aspartate transaminase 0 - 45 U/L

4. Amylase and/or lipase >3 x ULN

5. Bilirubin 6 - 24 mmol/L

6. Ferritin 15 - 200 ng/mL (females); 30 - 300 ng/mL (males)

7. Haemoglobin 115 - 155 g/L (females); 135 - 172 g/L (males)

- Subjects with a creatinine clearance cut-off of <50 ml/min

- Subjects requiring medication likely to influence blood pressure or gastrointestinal
function

- Subjects with a past history of gastrointestinal disease, including known
gastroparesis, significant upper gastrointestinal symptoms and previous gastric
surgery

- Subjects with a past history of unexplained pancreatitis, chronic pancreatitis,
pancreatectomy

- Subjects with a current or prior history of c-cell carcinoma

- Smoking > 10 cigarettes/day

- Alchohol consumption > 20 g/day

- Subjects who have donated blood in the previous 12 weeks

- Women of childbearing potential with no effective contraceptive method (defined as
premenopausal, not surgically sterile women for at least 3 months prior to the time of
screening) must have a confirmed negative urine B-hCG pregnancy test at screening
visit. They must also use an effective contraceptive method throughout the study, and
agree to repeat urine pregnancy test at designated visits.

- Lactation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2016
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Discipline of Medicine, Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
Royal Adelaide Hospital
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Sanofi
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
National Health and Medical Research Council, Australia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the effects of the drug lixisenatide on blood sugar
levels, stomach emptying, blood pressure and heart rate, release of gut hormones and blood
flow in the gut after a glucose drink in both healthy subjects and people with type 2
diabetes. If lixisenatide is shown to be effective, it would encourage ongoing evaluation of
its potential use in the management of the falls in blood pressure following a meal in
diabetic patients.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02308254
Trial related presentations / publications
Schirra J, Houck P, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut. 2000 May;46(5):622-31. doi: 10.1136/gut.46.5.622.
Brennan IM, Feltrin KL, Horowitz M, Smout AJ, Meyer JH, Wishart J, Feinle-Bisset C. Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men. Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1477-85. doi: 10.1152/ajpregu.00732.2004. Epub 2005 Feb 3.
Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, Schmiegel WH. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 1997 Nov;273(5):E981-8. doi: 10.1152/ajpendo.1997.273.5.E981.
Little TJ, Pilichiewicz AN, Russo A, Phillips L, Jones KL, Nauck MA, Wishart J, Horowitz M, Feinle-Bisset C. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. J Clin Endocrinol Metab. 2006 May;91(5):1916-23. doi: 10.1210/jc.2005-2220. Epub 2006 Feb 21.
Delgado-Aros S, Kim DY, Burton DD, Thomforde GM, Stephens D, Brinkmann BH, Vella A, Camilleri M. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol Gastrointest Liver Physiol. 2002 Mar;282(3):G424-31. doi: 10.1152/ajpgi.2002.282.3.G424.
Horowitz M, Nauck MA. To be or not to be--an incretin or enterogastrone? Gut. 2006 Feb;55(2):148-50. doi: 10.1136/gut.2005.071787.
Horowitz M, Rayner CK, Jones KL. Mechanisms and clinical efficacy of lixisenatide for the management of type 2 diabetes. Adv Ther. 2013 Feb;30(2):81-101. doi: 10.1007/s12325-013-0009-4. Epub 2013 Feb 13.
Riddle M, Home P, Marre M, Niemoeller E, Ping L, Rosenstock J. Efficacy and safety of once-daily lixisenatide in type 2 diabetes insufficiently controlled with basal insulin ± metformin: GetGoal-L Study. Diabetes 2012;61(Suppl 1):A212-A344 (Abstract 983-P).
Rosenstock J, Forst T, Aronson R, et al. Efficacy and safety of once-daily lixisenatide added on to titrated glargine plus oral agents in type 2 diabetes: GetGoal-Duo 1 Study. Presented at the 72nd Scientific Sessions of the American Diabetes Association, Philadelphia PA, 8-12 June 2012 (Abstract 62-OR).
Ahrén B, Dimas L, Miossec P, Saubado S, Aronson R. Efficacy and safety of lixisenatide QD morning and evening injections vs placebo in T2DM inadequately controlled on metformin (GetGoal-M). Oral presentation at the 21st World Diabetes Congress, Dubai, UAE, 8 December 2011 (Abstract 0-0591).
Ratner R, Hanefield M, Shamanna P, et al. Efficacy and safety of lixisenatide once daily versus placebo in patients with T2DM insufficiently controlled on sulfonylurea + metformin (GetGoal-S). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1):1-542 (Abstract 785).
Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Guo H, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab. 2013 Nov;15(11):1000-7. doi: 10.1111/dom.12121. Epub 2013 May 26.
Rosenstock J, Raccah D, Koranyi L, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in patients with T2DM insufficiently controlled on metformin (GetGoal-X). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1):1-542 (Abstract 786).
Bolli G, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Hanefield M. Efficacy and safety of lixisenatide once-daily versus placebo in patients with T2DM insufficiently controlled on metformin (GetGoal-F1). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1): 1-542 (Abstract 784).
Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE; EFC6018 GetGoal-Mono Study Investigators. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012 Jun;35(6):1225-31. doi: 10.2337/dc11-1935. Epub 2012 Mar 19.
Meier JJ, Kemmeries G, Holst JJ, Nauck MA. Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects. Diabetes. 2005 Jul;54(7):2212-8. doi: 10.2337/diabetes.54.7.2212.
Christensen M, Knop FK, Vilsboll T, Holst JJ. Lixisenatide for type 2 diabetes mellitus. Expert Opin Investig Drugs. 2011 Apr;20(4):549-57. doi: 10.1517/13543784.2011.562191. Epub 2011 Mar 11.
Jansen RW, Lipsitz LA. Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann Intern Med. 1995 Feb 15;122(4):286-95. doi: 10.7326/0003-4819-122-4-199502150-00009.
Shannon JR, Diedrich A, Biaggioni I, Tank J, Robertson RM, Robertson D, Jordan J. Water drinking as a treatment for orthostatic syndromes. Am J Med. 2002 Apr 1;112(5):355-60. doi: 10.1016/s0002-9343(02)01025-2.
Vanis L, Gentilcore D, Lange K, Gilja OH, Rigda RS, Trahair LG, Feinle-Bisset C, Rayner CK, Horowitz M, Jones KL. Effects of variations in intragastric volume on blood pressure and splanchnic blood flow during intraduodenal glucose infusion in healthy older subjects. Am J Physiol Regul Integr Comp Physiol. 2012 Feb 15;302(4):R391-9. doi: 10.1152/ajpregu.00464.2011. Epub 2011 Nov 30.
Jones KL, Tonkin A, Horowitz M, Wishart JM, Carney BI, Guha S, Green L. Rate of gastric emptying is a determinant of postprandial hypotension in non-insulin-dependent diabetes mellitus. Clin Sci (Lond). 1998 Jan;94(1):65-70. doi: 10.1042/cs0940065.
O'Donovan D, Feinle C, Tonkin A, Horowitz M, Jones KL. Postprandial hypotension in response to duodenal glucose delivery in healthy older subjects. J Physiol. 2002 Apr 15;540(Pt 2):673-9. doi: 10.1113/jphysiol.2001.013442.
Mathias CJ. Postprandial hypotension. Pathophysiological mechanisms and clinical implications in different disorders. Hypertension. 1991 Nov;18(5):694-704. doi: 10.1161/01.hyp.18.5.694. No abstract available.
Edwards CM, Todd JF, Ghatei MA, Bloom SR. Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects. Clin Sci (Lond). 1998 Dec;95(6):719-24. doi: 10.1042/cs0950719.
Barragan JM, Rodriguez RE, Eng J, Blazquez E. Interactions of exendin-(9-39) with the effects of glucagon-like peptide-1-(7-36) amide and of exendin-4 on arterial blood pressure and heart rate in rats. Regul Pept. 1996 Nov 14;67(1):63-8. doi: 10.1016/s0167-0115(96)00113-9.
White J. Efficacy and safety of incretin based therapies: clinical trial data. J Am Pharm Assoc (2003). 2009 Sep-Oct;49 Suppl 1:S30-40. doi: 10.1331/JAPhA.2009.09079.
Gentilcore D, Bryant B, Wishart JM, Morris HA, Horowitz M, Jones KL. Acarbose attenuates the hypotensive response to sucrose and slows gastric emptying in the elderly. Am J Med. 2005 Nov;118(11):1289. doi: 10.1016/j.amjmed.2005.05.019. No abstract available.
Stevens JE, Horowitz M, Deacon CF, Nauck M, Rayner CK, Jones KL. The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study. Aliment Pharmacol Ther. 2012 Aug;36(4):379-90. doi: 10.1111/j.1365-2036.2012.05198.x. Epub 2012 Jun 28.
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Jones KL, MacIntosh C, Su YC, Wells F, Chapman IM, Tonkin A, Horowitz M. Guar gum reduces postprandial hypotension in older people. J Am Geriatr Soc. 2001 Feb;49(2):162-7. doi: 10.1046/j.1532-5415.2001.49037.x.
Gentilcore D, Nair NS, Vanis L, Rayner CK, Meyer JH, Hausken T, Horowitz M, Jones KL. Comparative effects of oral and intraduodenal glucose on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects. Am J Physiol Regul Integr Comp Physiol. 2009 Sep;297(3):R716-22. doi: 10.1152/ajpregu.00215.2009. Epub 2009 Jun 24.
Gentilcore D, Hausken T, Meyer JH, Chapman IM, Horowitz M, Jones KL. Effects of intraduodenal glucose, fat, and protein on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects. Am J Clin Nutr. 2008 Jan;87(1):156-61. doi: 10.1093/ajcn/87.1.156.
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Public notes

Contacts
Principal investigator
Name 0 0
Karen L Jones, PhD
Address 0 0
University of Adelaide, Royal Adelaide Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Rachael S Tippett, BSc Honours
Address 0 0
Country 0 0
Phone 0 0
8222 2915
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02308254