| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Symptomatic treatment of constipation |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10010774 |
| E.1.2 | Term | Constipation |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. Quantitatively compare baseline corrected area under the
curve (AUCbaseline_c (0-180min)) [Baseline corrected area
under curve from 0 to 180 min for blood glucose
concentration (= Area under curve from 0 to 180 min minus
baseline*180min)], ie baseline corrected levels for blood
glucose after oral intake of Laevolac provided as
a) crystals at 20 and 30 g (medium size) and
b) liquid at 20 and 30 g
each compared to water.
2. Quantitatively compare increases in blood glucose
concentration after ingestion of 30 g Laevolac (crystals and
liquid) vs. 30 g glucose with regard to AUCbaseline_c (0-
180min) to show statistically significant lower blood
glucose levels in the Laevolac (crystals and liquid) group.
3. Quantitatively compare the AUCbaseline_c (0-180min) of
blood glucose concentration after intake of 20 g and 30 g
Laevolac crystals to the AUCbaseline_c (0-180min) after
intake of 20 g and 30 g Laevolac liquid. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patients with non-insulin requiring diabetes mellitus type 2 treated with diet and oral
antidiabetics and/or GLP-1 receptor agonists
2. Age: 18-75 years
3. Female and male
4. Caucasian
5. HbA1c ≤7.5 %
6. Stable treatment, i.e. no change in diabetes mellitus related medication within the last
3 months
7. Mild functional constipation according to modified Rome IV criteria fulfilled for the
last 3 months with symptom onset at least 6 months before study start defined as:
a. approx. 3-5 bowel movements per week,
b. of which 1-2 usually cause discomfort e.g., straining, lumpy or hard stools,
sensation of incomplete evacuation or anorectal obstructions/blockage
8. Availability and presence in the trial unit for approx. 4 hours/ week for 4 weeks
9. Women of childbearing potential must be using a medically approved method of
contraception OR women must be postmenopausal for at least 12 months prior to
study entry
10. Signed Informed Consent form |
|
| E.4 | Principal exclusion criteria |
1. Fasting blood glucose <4.4 mmol/L (<80 mg/dl) or >10 mmol/L (>180 mg/dL)
(capillary)
2. BMI <18.5 kg/m² or ≥35 kg/m²
3. Change in body weight ≥10 % within the last 3 months prior to randomization
4. Smoker
5. Major medical or surgical event requiring hospitalization within the last 3 months
prior to randomization
6. Acute gastrointestinal diseases including diarrhea and/or vomiting within the last 2
weeks prior to randomization
7. Presence of disease or intake of drug(s)/ supplements other than antidiabetic treatment
influencing digestion and absorption of carbohydrates or bowel habits (intake of
laxatives in general allowed with exception see next criterion) (dietary/ supplementary
fibres allowed if stable dose since 1 month before study start)
8. Not willing to abstain from laxatives 2 days before the visits 1-4 and up to 24h after
visits 1-4;
9. Use of following medication/supplementation within the last 4 weeks and during the
study:
a. Intake of medications other than antidiabetic treatment known to affect
glucose tolerance e.g., steroids, protease inhibitors or antipsychotics;
b. Intake of prebiotics or probiotics
c. Chronic intake of substances affecting blood coagulation (e.g. acetylsalicylic
acid (100 mg as standard prophylactic treatment allowed when dose is stable 1
month prior to screening), anticoagulants, diuretics, thiazides (diuretics and
thiazides allowed e.g. for hypertension treatment when dose is stable 1 month
prior to screening)), which in the investigator’s opinion would impact patient
safety
10. Severe liver, renal or cardiac disease
11. Hereditary problems of galactose or fructose intolerance, lactase deficiency or
glucose-galactose malabsorption
12. Suspicion of alcohol abuse (defined as an average daily intake of more than one litre
of beer per day or equivalent amount of alcohol in other beverages) or drug abuse
13. Known or suspected allergy to the investigational drug(s) or other components of the
study drug(s)
14. Acute inflammatory bowel disease (ulcerative colitis, Crohn's disease),
gastrointestinal obstruction or subocclusive syndrome, perforations or risk of
perforation in gastrointestinal tract, abdominal pain of undetermined cause
15. Known history of human immunodeficiency virus (HIV), hepatitis B and/or C
16. Pregnancy, lactation
17. Clinically relevant findings as established by medical history, physical examination,
clinical laboratory (see section 14.3.2 Laboratory Variables) and/or vital sign
(Screening failure)
18. Participation in another interventional study with an investigational drug or an
investigational medical device within 30 days prior to start of study or during the
study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Capillary blood glucose levels as baseline corrected AUC: AUCbaseline_c (0-180min)
[Baseline corrected area under curve from 0 to 180 min for blood glucose
concentration (= Area under curve from 0 to 180 min minus baseline*180 min)] |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Cmax: Maximum blood glucose concentration
Max_increase: Cmax minus baseline value
Max_increaserel: Cmax / baseline value
Tmax: Time to reach maximum blood glucose concentration
AUC(0-180min): Total area under curve from 0 to 180 min for blood glucose
concentration
iAUC(0-180min): Incremental area under curve from 0 to 180 min for blood glucose
concentration, i.e., above baseline levels for blood glucose concentration after oral
intake of Laevolac crystals/liquid or control products |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Laevolac liquid 20g and 30g, Laevolac crystals 20g and 30g, Glucose 30g, still water 250ml |
|
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LVLS +24h end of Observation time after LV |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
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