Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
sapropterin · 12 trials · 7 indications
Effects of 6R-BH4 on symptoms of ADHD in PKU subjects who had symptoms of ADHD at screening in the subjects that had a blood Phe level reduction after treatment with 6R-BH4. The total ADHD-RS score and the corrected total ARS score range from 0 to 54, with higher scores corresponding to worse severity of ADHD symptoms.
Effects of 6R-BH4 on global function in PKU subjects in subjects that had a blood Phe level reduction after treatment with 6R-BH4 at screening. The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children \>30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children \>6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests. FSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient.
Safety was assessed with regards to the rate and type of AEs, clinically significant changes to vital signs and/or physical examination findings, and clinically significant changes in laboratory test results.
Plasma BH4 concentration area under the curve (AUC0-12 hrs) at the end of each regimen in subjects with endothelial dysfunction.
A treatment-emergent adverse events (TEAE) is any adverse events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
This is to assess the effect of oral sapropterin dihydrochloride versus placebo on peak walking time (PWT) in subjects with intermittent claudication (IC) caused by peripheral arterial disease (PAD).
Adverse events were described and summarized with focus on treatment- emergent events (TEAEs). A TEAE was defined as any AE that presented , increased in frequency or worsened in severity following initiation of study drug administration. If the onset of an AE was missing then the AE was considered treatment emergent. Drug-related AEs are AEs classified by the investigator as possibly or probably related to study drug.
Identify dosing range of oral Kuvan® necessary and sufficient to normalize CSF BH4 levels in adults with GTPCH Deficiency.
| Arm | Type | Description |
|---|---|---|
| Sapropterin dihydrochloride | EXPERIMENTAL | - |
| Tablet without active ingredient | PLACEBO_COMPARATOR | - |
| Placebo | PLACEBO_COMPARATOR | Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study. |
| Sapropterin dihydrochloride+Vitamin C | EXPERIMENTAL | Sapropterin dihydrochloride 5 mg/kg and 500 mg Vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
| Kuvan Cohort 1 | EXPERIMENTAL | This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid. This cohort will begin at a dose of 20mg/kg/day. |
| Kuvan Cohort 2 | EXPERIMENTAL | Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1, but will plan on starting at 30 mg/kg/day. |
| 1 | EXPERIMENTAL | Open Label |
| Sapropterin Dihydrochloride 100mg/kg and placebo Moxifloxacin | EXPERIMENTAL | A single dose of 100mg/kg of Sapropterin Dihydrochloride taken along with placebo Moxifloxacin. |
| Sapropterin Dihydrochloride 20mg/kg and placebo Moxifloxacin | EXPERIMENTAL | A single dose of 20mg/kg of Sapropterin Dihydrochloride taken along with a placebo Moxifloxacin. |
| Sapropterin Dihydrochloride placebo and Moxifloxacin | ACTIVE_COMPARATOR | No placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with 400mg of Moxifloxacin. |
| Sapropterin Dihydrocholide placebo and Moxifloxacin placebo | PLACEBO_COMPARATOR | No placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with placebo of Moxifloxacin. |
| Name | Type | Description |
|---|---|---|
| Sapropterin dihydrochloride | DRUG | A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact). |
| Placebo | DRUG | Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study. |
| Sapropterin Dihydrochloride and Vitamin C | DRUG | Sapropterin Dihydrochloride 5 mg/kg and 500 mg Vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
| Sapropterin | DRUG | Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1. |
| sapropterin dihydrochloride (6R-BH4) | DRUG | 2.5 mg/kg/day for two weeks, 5 mg/kg/day for two weeks, 10 mg/kg/day for four weeks, then 20 mg/kg/day for two days |
| Moxifloxacin | DRUG | Moxifloxacin is included as a positive control to demonstrate the assay sensitivity based on the expected increased QTc response. |
| Moxifloxacin placebo | DRUG | Moxifloxacin placebo tablet |
Inclusion Criteria: * ≥ 8 years of age * Confirmed diagnosis of PKU * Willing to continue current diet (typical diet for the 3 months prior to study entry) unchanged while participating in the study * Willing and able to provide written, signed informed consent or in the case of subjects under the ...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| BioMarin Pharmaceutical Inc. | BMRN | 5 | PHASE3 | Pegvaliase |
| PTC Therapeutics, Inc. | PTCT | 2 | PHASE3 | PTC923 |
| Sanofi SA Sponsored ADR | SNY | 1 | PHASE1 | SAR444836 |
| Agios Pharmaceuticals, Inc. | AGIO | 1 | PHASE1 | AG-181 |
| Illumina, Inc. | ILMN | 1 | - | Undisclosed |
| Q32 Bio Inc | QTTB | 1 | - | HMI-102 |
Sapropterin is an investigational small molecule being studied for endothelial dysfunction, intermittent claudication, GTP cyclohydrolase deficiency, phenylketonuria, pulmonary arterial hypertension, and sickle cell disease. It is developed by BioMarin Pharmaceutical Inc. (BMRN) and is currently in Phase 2 clinical development.
Sapropterin is a synthetic form of tetrahydrobiopterin (BH4), a cofactor for enzymes involved in amino acid metabolism and nitric oxide synthesis. By providing BH4, it aims to restore enzyme function and improve nitric oxide production, which is relevant to its studied indications.
Sapropterin is developed by BioMarin Pharmaceutical Inc., a biopharmaceutical company traded on NASDAQ under the ticker BMRN. The company is conducting clinical trials to evaluate the drug for multiple conditions, including phenylketonuria and cardiovascular-related disorders.
Sapropterin is in Phase 2 clinical development. It has completed four trials, including Phase 1, Phase 2, and Phase 3 studies, with a total enrollment of 845 participants. No trials are currently active, and the drug remains investigational and not yet approved.
Sapropterin has completed four clinical trials: NCT00332189 (Phase 3 in phenylketonuria), NCT00532844 (Phase 2 in endothelial dysfunction), NCT00789568 (Phase 1 in healthy subjects), and NCT00838435 (Phase 3 in children with PKU). All trials are completed, with no active studies ongoing.
Sapropterin is also known as Kuvan, as referenced in the clinical trial NCT00838435, which evaluates the effect of Kuvan on neurocognitive function in children with PKU. The drug is developed by BioMarin Pharmaceutical Inc. under the brand name Kuvan.