Efficacy of domperidone (a prokinetic agent) on time in range in digestively asymptomatic type I diabetic patients with delayed gastric emptying

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2024-09-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the impact of prokinetic treatment of gastric emptying versus placebo on glycemic control defined by CGM (Continuous Glucose Monitoring) criteria in type 1 diabetic patients with delayed gastric emptying and digestively asymptomatic and insufficient glycemic control.

Secondary objectives 5

1. Determine the effect of domperidone on all glycemic control criteria.
2. Compare clinical and paraclinical determinants and glycemic parameters related to delayed gastric emptying between randomized and non-randomized patients (T1D patients with delayed gastric emptying who will be included in the intervention phase of the study versus patients with normal gastric emptying rate at the screening visit).
3. Evaluate tolerability of study treatment
4. Assess patient compliance with study treatment
5. Compare the percentages of patients achieving a mean 14-day T.I.R. (70-180 mg/dL) greater than 70% between the two groups.

Conditions and MedDRA coding

Type 1 Diabetic patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female ≥ 18 years and <75 years
2. Known type 1 diabetic patients for > 5 years treated with multi-injection insulin regimen or insulin pump with continuous interstitial glucose recording device (CGM) or closed loop
3. Type 1 diabetic patients with glycemic target TIR (70-180 mg/dL) < 60% and/or CV > 40% and/or early postprandial hypoglycemia, or at least 3 predictive pump stops in the postprandial period
4. Patient with few symptoms of gastroparesis based on GCSI score ≤ 2
5. Person who has read and understood the information letter and signed the consent form
6. Person affiliated to a social security scheme
7. A woman of childbearing potential (a woman is considered to be of childbearing potential fertile, after menarche and until she reaches menopause, unless she has reached the menopausal, unless she is definitively sterile) with at least effective contraception (i.e. at least: oral progestin-only hormonal contraception for which ovulation inhibition is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide). for at least 1 month and a negative urine B-HCG pregnancy test at inclusion
8. Surgically sterile women (hysterectomy, bilateral salpingectomy and bilateral oophorectomy)
9. Menopausal women: The postmenopausal state is defined as the absence of menstrual periods for 12 months without any other medical cause. An elevated follicle-stimulating hormone (FSH) level in the post-menopausal interval can be used to confirm a post-menopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months' amenorrhea, a single FSH measurement is insufficient

Exclusion criteria 14

1. Type 2 diabetic patients
2. Person taking part in another trial / having taken part in another therapeutic trial (study involving a drug or medical device) which could interfere with the products or procedures being investigated within a period of 4 weeks prior to inclusion
3. Any history of illness or psychological or sensory abnormality likely to prevent the subject from fully understanding the conditions required for participation in the protocol or from giving informed consent
4. history of bariatric surgery
5. Patients with CGM<70%
6. Type 1 diabetic patients with glycemic target TIR (70-180 mg/dL) < 20%
7. Patients with renal insufficiency (GFR<60 ml/min according to CKD-EPI formula), - Patients with contraindications to DOMPERIDONE ARROW 10 mg film-coated tablet: o Hypersensitivity to the active substance or to one of the excipients o Pituitary prolactin tumor (prolactinoma) o Underlying heart disease such as congestive heart failure (NYHA stage ≥2), o Kalemia less than 3.7 mmol/L or greater than 5.5 mmol/L, o Magnesemia less than 0.7 mmol/L o Hepatic impairment (TGO, TGP, GGT>2N, TP<70% (unless on anticoagulant)) o Known prolongation of cardiac conduction intervals, notably the QTc interval (QTc greater than 440 ms for men and greater than 460 ms for women) o Use of drugs that prolong the QTc interval (class IA antiarrhythmics (e.g. disopyramide, hydroquinidine, quinidine) and class III antiarrhythmics (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol), certain antipsychotics (e.g. haloperidol, pimozide, sertindole), certain antidepressants (e.g. citalopram, escitalopram), certain antibiotics (e.g. erythromycin, levifloxacin, moxifloxacin, spiramycin), certain antifungals (e.g. pentamidine, fluconazole), certain antimalarial drugs (in particular halofantrine, lumefantrine), certain digestive drugs (e.g. cisapride, dolasetron, prucalopride), certain antihistamines (e.g. mequitazine, mizolastine), certain anticancer drugs (e.g. toremifene, vandetanib, vincamine), certain other drugs (e.g. bepridil, diphemanil, methadone), apomorphine (unless the benefit of concomitant administration outweighs the risks, and only if the precautions recommended for concomitant administration are strictly observed). o Taking levodopa o Use of drugs that are potent or moderate inhibitors of CYP3A4: antiproteases, systemic azole antifungals, certain macrolide antibiotics (clarithromycin, telithromycin, azithromycin, roxithromycin, etc.), diltiazem, verapamil, etc. o Bradycardia (< 50 bpm) o Use of medication that induces bradycardia and hypokalemia o Presence of gastrointestinal bleeding, mechanical obstruction or digestive perforation o Lactose contraindication: galactose intolerance, total lactase deficiency, glucose-galactose malabsorption syndrome
8. Contraindication to gastric emptying test : - allergy to eggs, gluten, milk proteins, etc. - hepatic insufficiency - pulmonary diffusion disorders
9. Contraindication to placebo (calcium content): hypercalcemia/hypercalciuria, known calcium lithiasis
10. Pregnant, parturient or breast-feeding women, or those without proven effective contraception
11. Patients with contraindications to DOMPERIDONE ARROW 10 mg film-coated tablet: o Hypersensitivity to the active substance or to one of the excipients o Pituitary prolactin tumor (prolactinoma) o Underlying heart disease such as congestive heart failure (NYHA stage ≥2), o Kalemia less than 3.7 mmol/L or greater than 5.5 mmol/L, o Magnesemia less than 0.7 mmol/L o Hepatic impairment (TGO, TGP, GGT>2N, TP<70% (unless on anticoagulant)) o Known prolongation of cardiac conduction intervals, notably the QTc interval (QTc greater than 440 ms for men and greater than 460 ms for women) o Use of drugs that prolong the QTc interval (class IA antiarrhythmics (e.g. disopyramide, hydroquinidine, quinidine) and class III antiarrhythmics (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol), certain antipsychotics (e.g. haloperidol, pimozide, sertindole), certain antidepressants (e.g. citalopram, escitalopram), certain antibiotics (e.g. erythromycin, levifloxacin, moxifloxacin, spiramycin), certain antifungals (e.g. pentamidine, fluconazole), certain antimalarial drugs (in particular halofantrine, lumefantrine), certain digestive drugs (e.g. cisapride, dolasetron, prucalopride), certain antihistamines (e.g. mequitazine, mizolastine), certain anticancer drugs (e.g. toremifene, vandetanib, vincamine), certain other drugs (e.g. bepridil, diphemanil, methadone), apomorphine (unless the benefit of concomitant administration outweighs the risks, and only if the precautions recommended for concomitant administration are strictly observed). o Taking levodopa o Use of drugs that are potent or moderate inhibitors of CYP3A4: antiproteases, systemic azole antifungals, certain macrolide antibiotics (clarithromycin, telithromycin, azithromycin, roxithromycin, etc.), diltiazem, verapamil, etc. o Bradycardia (< 50 bpm) o Use of medication that induces bradycardia and hypokalemia o Presence of gastrointestinal bleeding, mechanical obstruction or perforation o Lactose contraindication: galactose intolerance, total lactase deficiency, glucose-galactose malabsorption syndrome o Confirmed or suspected pheochromocytoma due to the risk of severe episodes of hypertension
12. Person deprived of liberty by an administrative or judicial decision, or person under court protection, sub-guardianship or guardianship
13. patients with severe eating disorders
14. Patients receiving GLP-1 analog treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is the difference of percentages of time spent within the TIR glycemic target range (70-180 mg/dL) recorded over 14 days under prokinetic treatment (domperidone) or placebo in T1D patients with gastroparesis and inadequate glycemic control

Secondary endpoints 5

1. Variation in glycemic control criteria between domperidone and placebo (measurement of differences) o HbA1c assay o Plasma fructosamine assay, o number of hypoglycemic episodes, including severe ones, o percentage of time spent in hypoglycemia (<70mg/dL), o percentage of time spent in hyperglycemia (>180mg/dL), o coefficient of glycemic variability, o GMI o TIR, TBR, TAR, CV for each meal; o Insulin dose o Pre- and post-treatment gastric emptying data Tlag, T1/2
2. Clinical and paraclinical data in each group of T1D patients with or without delayed gastric emptying such as: -Age,sex,duration of diabetes,... -Total insulin dose,treatment modalities -Complications of diabetes: retinopathy,neuropathy,nephropathy,history of foot ulcers,vascular atheroma;cardiac,PAOD -VX neck,HbA1c,fructosamine,nb of hypoglycemic episodes,TIR,TBR,TAR,CV(overall & for each meal);GMI,GRI,blood glucose at start of emptying, 3-day weekly analysis, GCSI score
3. Number of AE and SAE
4. Number of times treatment/placebo taken (calculated from number of capsules returned by patient)
5. Ratio of time spent in target range (70-180 mg/dl) over 14 days per subject (in hours)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

MALLET

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

MALLET

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications