Study on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects

A Pilot, Phase 1, Randomized, Open-Label, Single-Dose, Four-Way Crossover Study to Compare the Pharmacokinetics of Sapropterin Dihydrochloride 100 mg/mL Oral Suspension (Product Code: RLF-OD032) (Test) With Kuvan® (Sapropterin Dihydrochloride) 100 mg Powder for Oral Solution (Reference) and to Evaluate the Effect of Food and the Effect of Water on the Bioavailability of Sapropterin Dihydrochloride 100 mg/mL Oral Suspension in Healthy Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06481709

Enrollment

Registered

2024-07-01

Start date

2024-07-30

Completion date

2024-08-31

Last updated

2025-06-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bioavailability

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. .

Detailed description

In each period, subjects will receive a single 10 mg/kg dose of sapropterin dihydrochloride on Day 1, under fasting or fed conditions, and with or without water, followed by 24 hours of PK sampling. The study will include a screening visit from Day -30 to Day -1. In each period, eligible subjects will be admitted to the clinical site on Day -1 and will be confined until completion of the assessments on Day 2. There will be a washout period of at least 7 days between doses.

Interventions

DRUGRLF-OD032

100 mg/mL oral suspension

DRUGKuvan

100 mg powder for oral solution

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

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

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

Inclusion criteria

1. 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. 2. Healthy as defined by: 1. the absence of clinically significant illness and surgery within 30 days prior to dosing. 2. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease. 3. Female subjects of non-childbearing potential must be: 1. 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 2. surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy or tubal ligation) at least 3 months prior to dosing. 4. Sexually active female subjects of childbearing potential must be willing to use an acceptable contraceptive method throughout the study as detailed in the protocol. 5. Willing to take off dentures or mouth piercing at the time of dosing. 6. Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion criteria

1. Any clinically significant abnormal finding at physical examination at screening. 2. 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. 3. Positive pregnancy test or lactating female subject. 4. Positive urine drug screen. 5. Known allergic reactions to sapropterin dihydrochloride or other related drugs, or to any excipient in the formulation. 6. 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. 7. 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. 8. History of alcohol addiction requiring treatment. 9. History of abuse of medicinal product or drugs within the last 3 years. 10. History or presence of alcoholism within the last 3 years. (\>40 g ethanol/day or more than 10 units per week \[1 unit =150 mL of wine, or 360 mL of beer, or 45 mL of 45% alcohol\]). 11. Use of medications within the timeframes specified in the protocol 12. 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. 13. Known predisposition to seizures. 14. 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. 15. 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. 16. Females who: 1. Have discontinued or changed the use of implanted, intrauterine, intravaginal, or injected hormonal contraceptives within 6 months prior to study treatment administration. 2. Have discontinued or changed the use of oral or patch hormonal contraceptives within 1 month prior to study treatment administration. 17. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Design outcomes

Primary

Measure	Time frame	Description
Uncorrected Sapropterin AUC0-t	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.	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
Baseline-corrected Sapropterin AUC0-t	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.	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
Uncorrected Sapropterin Cmax	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.	Maximum observed concentration
Baseline-corrected Sapropterin Cmax	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.	Maximum observed concentration
Uncorrected Sapropterin AUC0-inf	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.	Area under the concentration-time curve from time zero to infinity (extrapolated)
Baseline-corrected Sapropterin AUC0-inf	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.	Area under the concentration-time curve from time zero to infinity (extrapolated)

Countries

Canada

Participant flow

Participants by arm

Arm	Count
All Patients Included in the 4 Sequences (DCAB;ADBC;BACD;CBDA) Where the Subject receives these treatments according to the order of the assigned sequence 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. RLF-OD032: 100 mg/mL oral suspension Kuvan: 100 mg powder for oral solution	16
Total	16

Arm

Count

All Patients Included in the 4 Sequences (DCAB;ADBC;BACD;CBDA)

Where the Subject receives these treatments according to the order of the assigned sequence 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. RLF-OD032: 100 mg/mL oral suspension Kuvan: 100 mg powder for oral solution

Total

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Withdrawal by Subject	0	0	2	0

Baseline characteristics

Characteristic	All Patients Included in the 4 Sequences (DCAB;ADBC;BACD;CBDA)
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	16 Participants
Age, Continuous	31 years STANDARD_DEVIATION 10
BMI	25 kg/m^2 STANDARD_DEVIATION 4
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	5 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	4 Participants
Region of Enrollment Canada	16 participants
Sex: Female, Male Female	7 Participants
Sex: Female, Male Male	9 Participants
weight	70.4 kg STANDARD_DEVIATION 10.3

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 16	0 / 14	0 / 14
other Total, other adverse events	1 / 16	1 / 16	2 / 14	0 / 14
serious Total, serious adverse events	0 / 16	0 / 16	0 / 14	0 / 14