A Phase 2 interventional study of PF-06801591 in HFI, sponsored by Maastricht University Medical Center. Completed at 1 site in Netherlands. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-01-24.
Sponsored by Maastricht University Medical Center · Phase 2, Interventional, and Treatment
Hereditary fructose intolerance (HFI) is a rare inborn error of metabolism. Patients with HFI develop acute abdominal pain, nausea, vomiting, hypoglycemia and proximal tubular dysfunction upon consumption of a fructose containing food product. In rare cases, (prolonged) fructose consumption can even lead to liver and kidney failure. Patients with HFI are therefore treated with a lifelong fructose-restricted diet. Animal studies have shown that the clinical manifestations of HFI are abrogated upon inhibition of ketohexokinase (KHK), the enzyme that catalyses the first step in fructose metabolism.
Recently, PF-06835919, a KHK inhibitor (KHKi), was developed as a new treatment for non-alcoholic fatty liver disease. The compound was well tolerated in several phase II clinical trials.
It is hypothesized that PF-06835919 is also effective in patients with HFI.
Rationale: Hereditary fructose intolerance (HFI) is a rare inborn error of metabolism. Patients with HFI develop acute abdominal pain, nausea, vomiting, hypoglycemia and proximal tubular dysfunction upon consumption of a fructose containing food product. In rare cases, (prolonged) fructose consumption can even lead to liver and kidney failure. Patients with HFI are therefore treated with a lifelong fructose-restricted diet. Animal studies have shown that the clinical manifestations of HFI are abrogated upon inhibition of ketohexokinase (KHK), the enzyme that catalyses the first step in fructose metabolism.
Recently, PF-06835919, a KHK inhibitor (KHKi), was developed as a new treatment for non-alcoholic fatty liver disease. The compound was well tolerated in several phase II clinical trials.
It is hypothesized that PF-06835919 is also effective in patients with HFI. Objective: To study the effects of PF-06835919 on fructose tolerance and intrahepatic lipid content in patients with HFI. Study design: open-label, pilot study Study population: three adult patients with HFI will be treated with PF-06835919. Five adult healthy individuals will be included (but not be treated) as a reference. Intervention (if applicable): Patients receive once daily (in the morning) three tablets of 100 mg PF-06835919 for 9 days. They will subsequently be gradually exposed to increasing doses of either oral fructose or glucose (in a blinded fashion). Healthy individuals will only undergo oral fructose exposure, as a reference. Main study parameters/endpoints: Intrahepatic lipid content assessed by proton magnetic resonance spectroscopy (at baseline and completion), intestinal fructose tolerance (after oral fructose in comparison to oral glucose), hepatic fructose tolerance (serum glucose and phosphate after oral fructose in comparison to healthy individuals) and renal fructose tolerance (urinary glucose, phosphate, pH and amino acids after oral fructose in comparison to healthy individuals). Nature and extent
Inclusion Criteria:
Exclusion Criteria:
Subjects who do not want to be informed about unexpected medical findings
HFI participants will receive PF-06835919 for 9 days. Dosage; once daily 300 mg PF-06835919 in the form of 3 tablets, oral.
Drug: PF-06801591
Healthy controls will receive no intervention, but a single fructose tolerance test.
Active ketohexokinase inhibitor
Also known as: KHKi
Intestinal Fructose tolerance,
a visual analog scale from 1-10 for abdominal pain will be used. Additional every 5 minutes the participant will be asked if he/she is nauseous, and more, less or similar nauseous as 5 minutes before.
Time frame: 9 days
Intestinal Fructose tolerance,
Every 5 minutes the participant will be asked if he/she is nauseous, and more, less or similar nauseous as 5 minutes before.
Time frame: 9 days
Renal Fructose tolerance
Urinary pH
Time frame: 9 days
Renal Fructose tolerance
Glucose content, mmol/L
Time frame: 9 days
Renal Fructose tolerance
Phosphate content mmol/L
Time frame: 9 days
Renal Fructose tolerance
Amino acid content mmol/L
Time frame: 9 days
Hepatic fructose tolerance
Serum glucose levels, mmol/L
Time frame: 9 days
Hepatic fructose tolerance
Serum phosphate levels, mmol/L
Time frame: 9 days
Intrahepatic lipid content
measured using 1H-MRS at baseline and completion
Time frame: 9 days
Blood pressure
measured at baseline and completion. Both systolic and diastolic pressure will be assessed
Time frame: 9 days
Glycosylated transferrin
measured at baseline and completion.
Time frame: 9 days
Plan to share: No — Data can be obtained with the PI on request
No publications or documents are linked to this record.
This study is completed, as verified in Jan 2024. You cannot join it, but the record below documents what was studied.
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Fructose Intolerance
Maastricht University Medical Center