E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-bariatric hypoglycaemia |
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E.1.1.1 | Medical condition in easily understood language |
Low blood glucose in patients submitted to bariatric surgery. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
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 |
To investigate whether canagliflozin/acarbose therapy is an effective treatment for post-bariatric hypolgycaemia (PBH). |
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E.2.2 | Secondary objectives of the trial |
To explore how chronic treatment with canagliflozin/acarbose modulates the response to a standard meal; To clarify if there is a correlation between PBH symptomatology, glycaemic variability and electrocardiographic findings, and whether these are modulated by treatment interventions.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At enrolment, participants must: • Be adults (above 18 years old); • Have undergone bariatric surgery more than 18 months prior to inclusion; • Self-reported weight stability (less than 5% variation over the 6 months); • Present at least one 5-minutes or longer event of interstitial fluid glucose <3.0 mmol/L, one 5-minutes symptomatic event of IFG<3.9mmol/L (allowing a time gap between symptoms reported and low glucose values of ±30 minutes) at least 4.0% of IFG <3.9mmol/L during a min 10 days CGM monitoring screening period, excluding first 24 hours of monitoring (prone to error due to local inflammatory reaction); • Have a negative pregnancy test, if applicable; • Commit to safe contraception during the trial and over the following 5 months, namely intrauterine devices, hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections) or double barrier methods (a condom combined with a diaphragm). |
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E.4 | Principal exclusion criteria |
All patients presenting one of the following at enrolment will be excluded: • Altered baseline analytical profile, namely an early morning 12h-fasting blood test with hemogram, liver and kidney functions tests, albumin, total proteins, plasma glucose, TSH, insulin, C-peptide, and beta-hCG and thus pointing towards other potential causes for hypoglycaemia and/or prone to unsafety to pursue the trial*; • Inability or unwillingness to perform meal test (e.g. unable to have the meal over 20 minutes); • Pharmacotherapy that affects glucose metabolism: • Glucocorticoid treatment within 6 weeks of inclusion; • Somatostatin analogue treatment within 4 months of inclusion; • GLP-1 receptor analogue treatment within 6 half-lives of inclusion; • SGLT2 inhibitor treatment within 2 weeks of inclusion. • HbA1c >47.5 mmol/mol [>6.5%;] • Antithyroid treatment within 3 months of inclusion or poorly managed thyroid disease (TSH outside reference range); • Pregnancy (positive pregnancy test), aspiring to get pregnant over the following 5 months or lactation; • Renal insufficiency (eGFR <60 ml/min/1.73m2); • Elevation of liver enzymes (>3 x elevation of upper normal limit of alanine amino transferase and/or alkaline phosphatases); • Poorly controlled psychiatric disease or mental retardation; • Alcohol or other substance abuse; • Significant anaemia (Hb <6.0 mmol/L); • Recent history of major adverse cardiovascular events (MACE), such as hospitalizations for heart failure, nonfatal stroke, or nonfatal myocardial infarction within the previous 12 months; • Any other condition that in the opinion of the investigator may compromise outcome; • Sustained intolerance to study drugs. |
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E.5 End points |
E.5.1 | Primary end point(s) |
o Time under level 1 hypoglycaemia (IFG <3.9 mmol/L or <70 mg/dL) throughout CGM evaluation, comparing treatment intervention A (canagliflozin) and B (acarbose) against treatment intervention C (placebo). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Last 10-14 days of each treatment intervention. |
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E.5.2 | Secondary end point(s) |
- Time under level 2 hypoglycaemia (IFG <3.0 mmol/L or <54 mg/dL) throughout CGM evaluation, comparing treatment interventions A and B against C; - Postprandial nadir glucose during the meal test, comparing treatment interventions A and B against C; |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Last 10-14 days of each treatment intervention. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.6 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 | Yes |
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
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Last visit of the last subject undergoing the trial. |
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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 | |
E.8.9.1 | In the Member State concerned days | |