E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Hereditary fructose intolerance | Hereditaire fructose intolerantie | |
E.1.1.1 | Medical condition in easily understood language | fructose intolerance | fructose intolerantie | |
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 | 10019878 | E.1.2 | Term | Hereditary fructose intolerance | 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 | LLT | E.1.2 | Classification code | 10017397 | E.1.2 | Term | Fructose intolerance hereditary | 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 | 21.0 | E.1.2 | Level | PT | E.1.2 | Classification code | 10072104 | E.1.2 | Term | Fructose intolerance | E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition 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 assess the effects of short-term treatment with PF-06835919 on intestinal, hepatic and renal fructose tolerance, and intrahepatic lipid content in patients with hereditary fructose tolerance | Het bepalen van het effect van de ketohexokinase remmer, PF-06835919, op fructose tolerantie in de darmen, lever en nieren in patiënten met hereditaire fructose intolerantie | |
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | -Participants are able to provide signed and dated written informed consent prior to any study specific procedures -Use of effective contraception (only applicable to premenopausal women; a pregnancy test will be performed in these women at baseline) -Aged ≥ 18 years -Hereditary fructose intolerance, diagnosed by either genetic testing, liver biopsy or intravenous fructose tolerance test* *Not applicable for healthy controls | -Deelnemers zijn in staat om ondertekende en gedateerde geschreven geïnformeerde toestemming te verschaffen voorafgaand enige studie specifieke procedures -Leeftijd ≥ 18 jaar -Gebruik van effectieve contraceptie (alleen toepasselijk op premenopausale vrouwen; een zwangerschapstest zal gedaan worden bij deze vrouwen bij baseline). -Hereditaire fructose intolerantie, gediagnostiseerd door genetische testen, leverbiopt of intraveneuze fructose tolerantie test* *niet toepasselijk op de gezonde controles | |
E.4 | Principal exclusion criteria | -Diabetes Mellitus -Any contra-indication for MRI scanning* -Patients with congestive heart failure and and/or severe renal and/or liver insufficiency -Uncontrolled hypertension -Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator which would possibly hamper our study results -Use of drugs that inhibit organic anion transporting polypeptide B1 (OATPB1) transporters (e.g. rifampicin, gemfibrozil, cyclosporine, erythromcyin and clarithromycin)* -Subjects who do not want to be informed about unexpected medical findings -Pregnancy* -Treatment with irinotecan* *only applicable for HFI patients | -Diabetes Mellitus -Elke contra-indicatie voor MRI scans* -Patiënten met congestief hartfalen en/of ernstige nierfalen en/of leverfalen -ongecontroleerde hypertensie -Deelname aan een klinische studie met een onderzoeksproduct in de voorafgaande 3 maanden, of als zodanig beoordeeld door de onderzoeker, die onze resultaten kan beïnvloeden -Medicatie gebruik dat organisch anion transporterend polypeptide B1 (OATPB1) transporters blokkeert (e.g. gemfibrozil, cyclosporine, erythromcyin en clarithromycin)* -Deelnemers die niet willen worden geïnformeerd over onverwachte medische bevindingen -Zwangerschap* -Behandeling met irinotecan* *Alleen toepasselijk voor HFI patiënten | |
E.5 End points |
E.5.1 | Primary end point(s) | The primairy endpoint is fructose tolerance, assessed at the level of the intestines (abdominal complaints), liver (serum glucose and phosphate levels) and kidney (urinary pH, glucose, phosphate and amino acids) | De primaire uitkomstmaat is fructose tolerantie, beoordeeld op het niveau van de darmen (abdominale klachten), lever (serum glucose en fosfaat concentraties), en nier (pH-graad van urine, fosfaat en amino zuren). | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | The primary endpoint will be evaluated every testday, after either a glucose or fructose tolerance test. | De primaire uitkomstmaat zal elke testdag worden beoordeeld na een glucose of fructose tolerantie test. | |
E.5.2 | Secondary end point(s) | The secondary endpoints are: -Intrahepatic lipid content (measured using 1H-MRS at baseline and completion) -Blood pressure (measured at baseline and completion) -Glycosylated transferrin (measured at baseline and completion) | De secundaire uitkomstmaten zijn: - Hoeveelheid levervet (gemeten met 1H-MRS) op baseline en na voltooiing van de volledige 9 dagen medicatie - Bloeddruk op baseline en na voltooiing van de volledige 9 dagen - Glycosylated transferrin op baseline en na voltooiing van de volledige 9 dagen | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | The secondary endpoints will be evaluated at baseline, and after participants have taken PF-06835919 daily for 9 days. | De secundaire uitkomstmaten zullen worden beoordeeld op baseline en nadat deelnemers PF-06835919 dagelijks voor 9 dagen. | |
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 | The trial involves single site in the Member State concerned | No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | 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 | |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |