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Study on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects Under Fed Conditions

A

APR Applied Pharma Research

Status and phase

Not yet enrolling
Phase 1

Conditions

Bioequivalence

Treatments

Drug: RLF-OD032 100 mg/mL oral suspension
Drug: Kuvan 100 MG Powder for Oral Solution

Study type

Interventional

Funder types

Other

Identifiers

NCT06987773
2024-5705

Details and patient eligibility

About

This is a single center, Phase 1, randomized, open-label, single-dose, 2 treatment, 2-period,2-sequence, crossover study designed to compare the pharmacokinetics (PK) of sapropterin between the Test and Reference products in healthy Participants.

Full description

In each period, subjects will receive a single 10 mg/kg dose of sapropterin dihydrochloride on Day 1, under fed conditions, 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.

Enrollment

100 estimated patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  1. Healthy male or female participants, light smokers (no more than 10 cigarettes daily) or non-smokers, from 18 to 50 years of age.

  2. BMI ≥18.5 and ≤30 kg/m2 and weight ≥50.0 and ≤100.0 kg for males and ≥45.0 and ≤100.0 kg for females

  3. Females may be of childbearing or non-childbearing potential:

    • Childbearing potential:
    • Physically capable of becoming pregnant
    • Non-childbearing potential:
    • Surgically sterile (i.e., both ovaries removed, uterus removed, or bilateral tubal ligation) at least three (3) months prior to first drug administration; and/or;
    • Postmenopausal (no menstrual period for at least 12 consecutive months without any other medical cause and a FSH value consistent with being postmenopausal).
  4. Willing to use acceptable, effective methods of contraception.

  5. Able to tolerate venipuncture.

  6. Be informed of the nature of the study and give written consent prior to any study procedure.

Exclusion criteria

  1. History of clinically significant neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the participant or impact the validity of the study results.

  2. Clinically significant illness and/or surgery.

  3. Known or suspected carcinoma.

  4. History of hypersensitivity or idiosyncratic reaction to sapropterin dihydrochloride or any other drug substances with similar activity.

  5. History of or predisposition to seizure which, in the opinion of the Investigator, would jeopardize the safety of the participant or impact the validity of the study results.

  6. History of upper gastrointestinal (GI) mucosal inflammation, esophagitis, gastritis, pharyngitis, or oropharyngeal pain, which, in the opinion of the Investigator, would jeopardize the safety of the participant or impact the validity of the study results.

  7. History of abuse of medicinal product or drugs within the last three (3) years.

  8. History of alcohol addiction requiring treatment.

  9. History or presence of alcoholism within the last three (3) years. (>40 g ethanol/day or >10 units per week [one (1) unit =150 mL of wine, or 360 mL of beer, or 45 mL of 45% alcohol])

  10. History of recreational use of soft drugs (such as marijuana) within one (1) month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within three (3) months prior to screening.

  11. Use of St. John's wort within 30 days prior to the first drug administration.

  12. History of clinically significant lactose, galactose, or fructose intolerance.

  13. Presence of hepatic or renal dysfunction.

  14. Presence of mouth piercings (object or hole), presence of non-removable dentures and orthodontic appliances (e.g., braces, retainers), or any other alteration to the mouth that may be deemed by the Investigator to compromise drug delivery.

    Note: Dental fillings, crowns, bridges, and implants are permitted as they are not considered to compromise drug delivery.

  15. History of malabsorption within the last year or presence of clinically significant gastrointestinal (GI) disease.

  16. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption.

  17. Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.

  18. Positive test result for urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants).

  19. Difficulty fasting or consuming high-fat, high-calorie or standard meals.

  20. Regularly smokes more than 10 cigarettes per day within 6 months prior to the first drug administration.

  21. Participants who received an implanted or injected (depot injection) medication, including hormonal contraceptives, within three (3) months prior to the first drug administration.

  22. Females who:

    • Have discontinued or changed the use of implanted, intrauterine, intravaginal, or injected hormonal contraceptives within six (6) months prior to the first drug administration;
    • Have discontinued or changed the use of oral or patch hormonal contraceptives within one (1) month prior to the first drug administration;
    • Are pregnant (serum β-hCG consistent with pregnancy); or
    • Are breast-feeding.
  23. Donation or loss of whole blood (including clinical trials):

    • ≥50 mL and <500 mL within 30 days prior to the first drug administration; or
    • ≥500 mL within 56 days prior to the first drug administration.
  24. Donation of plasma within seven (7) days prior to dosing.

  25. Participation in a clinical trial that involved administration of a biological product within 90 days prior to the first drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize participant safety or the integrity of the study results.

  26. Participation in a clinical trial that involved administration of an investigational medicinal product, marketed drug or device within 30 days prior to the first drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize participant safety or the integrity of the study results.

  27. On a special diet within 30 days prior to the first drug administration (e.g., liquid, protein, raw food diet).

  28. Have had a tattoo or body piercing within 30 days prior to the first drug administration.

  29. Have clinically significant findings in vital signs measurements and systolic blood pressure (SBP) <90 mmHg or >150 mmHg and diastolic blood pressure (DBP) <50 or >90 mmHg, or PR <50 or >100 bpm). Vitals signs may be repeated up to two (2) times, to determine if the values are significantly abnormal.

  30. Have clinically significant findings in a 12-lead ECG. ECG readings may be repeated up to two times, to determine if the values are significantly abnormal.

  31. Have clinically significant abnormal laboratory values. Laboratory tests may be repeated up to two (2) times, to determine if the values are significantly abnormal.

  32. Have significant diseases.

  33. Use of any of the following drugs within 30 days prior to drug administration:

    • Breast cancer resistance protein (BCRP) substrates (e.g., rosuvastatin);
    • Drugs affecting nitric oxide-mediated vasorelaxation (e.g., PDE-5 inhibitors, sildenafil, vardenafil, or tadalafil);
    • Folate synthesis inhibitors (e.g. methotrexate, valproic acid, phenobarbital, or trimethoprim);
    • Levodopa; or
    • Drugs which alter GI pH/movement (e.g., omeprazole, ranitidine).
  34. Use of vaccine including COVID-19 vaccine within 14 days prior to the first drug administration.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

None (Open label)

100 participants in 2 patient groups

AB
Other group
Description:
A) A single 10 mg/kg dose of a 100 mg/mL oral suspension of sapropterin dihydrochloride (RLF-OD032) , administered under fed conditions without water followed by B) A single 10 mg/kg dose of a 100 mg powder for oral solution of the Reference Product (Kuvan) , dissolved in water, administered under fed conditions with water
Treatment:
Drug: Kuvan 100 MG Powder for Oral Solution
Drug: RLF-OD032 100 mg/mL oral suspension
BA
Other group
Description:
B) A single 10 mg/kg dose of a 100 mg powder for oral solution of the Reference Product (Kuvan) , dissolved in water, administered under fed conditions with water followed by A) A single 10 mg/kg dose of a 100 mg/mL oral suspension of sapropterin dihydrochloride (RLF-OD032), administered under fed conditions without water
Treatment:
Drug: Kuvan 100 MG Powder for Oral Solution
Drug: RLF-OD032 100 mg/mL oral suspension

Trial contacts and locations

0

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Central trial contact

Giorgio Reiner

Data sourced from clinicaltrials.gov

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