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

Inclusion Criteria

• Healthy male or female participants, light smokers (no more than 10 cigarettes daily) or non-smokers, from 18 to 50 years of age.
• 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
• 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).
• Willing to use acceptable, effective methods of contraception.
• Able to tolerate venipuncture.
• Be informed of the nature of the study and give written consent prior to any study procedure.

Exclusion Criteria

• 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.
• Clinically significant illness and/or surgery.
• Known or suspected carcinoma.
• History of hypersensitivity or idiosyncratic reaction to sapropterin dihydrochloride or any other drug substances with similar activity.
• 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.
• 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.
• History of abuse of medicinal product or drugs within the last three (3) years.
• History of alcohol addiction requiring treatment.
• 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])
• 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.
• Use of St. John's wort within 30 days prior to the first drug administration.
• History of clinically significant lactose, galactose, or fructose intolerance.
• Presence of hepatic or renal dysfunction.
• 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.

• History of malabsorption within the last year or presence of clinically significant gastrointestinal (GI) disease.
• Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption.
• Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
• Positive test result for urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants).
• Difficulty fasting or consuming high-fat, high-calorie or standard meals.
• Regularly smokes more than 10 cigarettes per day within 6 months prior to the first drug administration.
• Participants who received an implanted or injected (depot injection) medication, including hormonal contraceptives, within three (3) months prior to the first drug administration.

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