E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cori Forbe's Disease
Also called: glycogen storage disease Type III or debrancher deficiency.
Tarui's disease
Also called: glycogen storage disease Type VII or phosphofructokinase deficiency.
Glycogenin-1 deficiency or glycogen storage disease Type XV.
|
|
E.1.1.1 | Medical condition in easily understood language |
GSD III and GSD XV are inborn genetic defects in muscle cells causing deficient glycogen metabolism.
GSD VII is a genetic defect in muscle cells causing deficient glucose metabolism. |
GSD III, GSD VII og GSD XV er medfødte gendefekter i muskler, hvilket medfører enten nedsat glykogenforbrænding eller nedsat glukoseforbrænding i muskelcellerne. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053241 |
E.1.2 | Term | Glycogen storage disease type VII |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053250 |
E.1.2 | Term | Glycogen storage disease type III |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053255 |
E.1.2 | Term | Tarui disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016983 |
E.1.2 | Term | Forbes' disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of Triheptanoin on fatty acid oxidation and exercise tolerance in patients with debrancher deficiency, glycogenin-1 deficiency and phosphofructokinase deficiency at rest and during exercise.
|
|
E.2.2 | Secondary objectives of the trial |
To investigate the effect of Triheptanoin treatment on:
* Self-rated daily function scores on a modified SF-36 questionnaire
* Maximal workload capacity (Wmax).
* Changes in plasma concentrations of lactate, ammonia, glucose, FFA, acyl-carnitines, malate (a TCA intermediate), C5, and hormones.
* Rate of Perceived Exertion (Borg score) during constant workload cycling.
* Maximal oxidative capacity.
* Bouchards energy expenditure questionnaire.
* Glucose rate of appearance and disappearance.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male/Female Age > 15 years
- Genetically and/or biochemically verified diagnosis of GSD III, GSD VII or GSD XV
- Capacity to consent
- For women in fertile age on contraceptive treatment with: Birth control
pills, coil, ring, transdermal hormone patch injection of gestagen or
subdermal implant. |
|
E.4 | Principal exclusion criteria |
- Significant cardiac or pulmonary disease
- Pregnancy (confirmed by urine stix or plasma-HCG) or breastfeeding.
- Inability to perform cycling exercise
- Any other significant disorder that may confound the interpretation of
the findings |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Heart rate during constant load cycling exercise (HR_const)
- Fatty acid oxidation (FAO) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before and after 14 days of treatment with Triheptanoin and before and
after 14 days of placebo treatment. |
|
E.5.2 | Secondary end point(s) |
• Self-reported health and well-being addressed in an SF-36 Questionnaire.
• Maximal workload capacity (Wmax).
• Plasma concentrations of lactate, ammonia, glucose, FFA, acyl-carnitines and malate (a TCA intermediate), creatine kinase, and hormones.
• Rate of Perceived Exertion during constant workload cycling (RPEconst).
• Total fatty acid oxidation and total carbohydrate oxidation measured by indirect calorimetry.
• Glucose rate of appearance and disappearance.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before and after 14 days of treatment with Triheptanoin and before and after 14 days of placebo treatment. |
|
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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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
|
When all data is collected and the last safety follow-up has been done |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 31 |