Study on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects

NCT06481709 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2023-5439
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, Phase 1, randomized, open-label, single-dose, 4 treatment, 4-period, 4-sequence, crossover study designed to compare the pharmacokinetics (PK) of sapropterin from the Test and Reference products, and to evaluate the effect of food and the effect of water administration on the bioavailability of sapropterin from the Test product in healthy subjects. .

Conditions

Bioavailability

Outcome Measures

Primary Outcomes (6)

• Uncorrected Sapropterin AUC0-t

  Area under the concentration-time curve from time zero until the last observed concentration, as calculated by the linear up/log down variant of the trapezoidal method

  Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.

• Baseline-corrected Sapropterin AUC0-t

  Area under the concentration-time curve from time zero until the last observed concentration, as calculated by the linear up/log down variant of the trapezoidal method

  Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.

• Uncorrected Sapropterin Cmax

  Maximum observed concentration

  Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.

• Baseline-corrected Sapropterin Cmax

  Maximum observed concentration

  Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.

• Uncorrected Sapropterin AUC0-inf

  Area under the concentration-time curve from time zero to infinity (extrapolated)

  Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.

• Baseline-corrected Sapropterin AUC0-inf

  Area under the concentration-time curve from time zero to infinity (extrapolated)

  Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.

Study Arms (4)

Sequence DCAB

OTHER

Where the Subject receives in this order D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions. A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions. B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.

Drug: RLF-OD032; Drug: Kuvan

Sequence ADBC

OTHER

Where the Subject receives in this order A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions. D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions. C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.

Drug: RLF-OD032; Drug: Kuvan

Sequence BACD

OTHER

Where the Subject receives in this order B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions. A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions. C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions. D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions

Drug: RLF-OD032; Drug: Kuvan

Sequence CBDA

OTHER

Where the Subject receives in this order C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions. B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions. D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.

Drug: RLF-OD032; Drug: Kuvan

Interventions

RLF-OD032 DRUG

100 mg/mL oral suspension

Also known as: Sapropterin dihydrochloride

Sequence ADBC; Sequence BACD; Sequence CBDA; Sequence DCAB

Kuvan DRUG

100 mg powder for oral solution

Also known as: Sapropterin dihydrochloride

Sequence ADBC; Sequence BACD; Sequence CBDA; Sequence DCAB

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female, light smoker (no more than 10 cigarettes daily) or non smoker, ≥18 and ≤50 years of age, with body mass index (BMI) ≥18.5 and ≤30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
• Healthy as defined by:
• the absence of clinically significant illness and surgery within 30 days prior to dosing.
• the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
• Female subjects of non-childbearing potential must be:
• post-menopausal (no menstrual period at least 12 consecutive months without any other medical cause and FSH and LH values consistent with being menopausal); or
• surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy or tubal ligation) at least 3 months prior to dosing.
• Sexually active female subjects of childbearing potential must be willing to use an acceptable contraceptive method throughout the study as detailed in the protocol.
• Willing to take off dentures or mouth piercing at the time of dosing.
• Able to understand the study procedures and provide signed informed consent to participate in the study.

You may not qualify if:

• Any clinically significant abnormal finding at physical examination at screening.
• Clinically significant abnormal laboratory test results (may be repeated up to two times) or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV)-1 and HIV-2 antibodies at screening.
• Positive pregnancy test or lactating female subject.
• Positive urine drug screen.
• Known allergic reactions to sapropterin dihydrochloride or other related drugs, or to any excipient in the formulation.
• Clinically significant ECG abnormalities or vital signs abnormalities (systolic blood pressure lower than 90 or over 150 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or pulse rate less than 50 or over 100 bpm) at screening. ECG and vitals signs may be repeated up to two times, to determine if the values are significantly abnormal.
• Recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
• History of alcohol addiction requiring treatment.
• History of abuse of medicinal product or drugs within the last 3 years.
• History or presence of alcoholism within the last 3 years. (\>40 g ethanol/day or more than 10 units per week \[1 unit =150 mL of wine, or 360 mL of beer, or 45 mL of 45% alcohol\]).
• Use of medications within the timeframes specified in the protocol
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to dosing, administration of a biological product in the context of a clinical research study within 90 days prior to dosing, or concomitant participation in an investigational study involving no drug or device administration.
• Known predisposition to seizures.
• Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
• Presence of orthodontic braces or orthodontic retention wires, or any physical findings in the mouth or tongue that would be likely to interfere with successful completion of the dosing procedure.

Sponsors & Collaborators

• APR Applied Pharma Research s.a.: lead

Study Sites (1)

Pharma Medica Research Inc. 4770 Sheppard Ave E,

Toronto, Ontario, M1S3V6, Canada

Location

MeSH Terms

Interventions

sapropterin

Results Point of Contact

• Title: Giorgio Reiner Chief Scientific Officer
• Organization: APR Applied Pharma Research s.a.

giorgio.reiner@apr.ch

+41.91.6957020

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In each period, subjects will receive one of the following treatments, according to the randomization scheme: Treatment A: 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions. Treatment B: 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions. Treatment C: 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions. Treatment D: 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions

Study Record Dates

• First Submitted: June 6, 2024
• First Posted: July 1, 2024
• Study Start: July 30, 2024
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: June 12, 2025
• Results First Posted: June 12, 2025

Record last verified: 2023-11

Locations

CA (1)