A Phase 1 Study to Evaluate Effects of Sapropterin Dihydrochloride on QTc Intervals in Healthy Adult Subjects

Completed · Phase 1 · Has a placebo group

Conditions studied: Phenylketonuria

In brief

Sapropterin dihydrochloride (subsequently referred to as sapropterin) (Kuvan®) was approved by the FDA for the treatment of hyperphenylalaninemia in 2007. Preclinical and clinical studies and post-marketing surveillance have not demonstrated any specific cardiovascular concerns with sapropterin (Kuvan®). Nonetheless, nonantiarrhythmic drugs may have the potential to prolong QT interval, leading to potentially fatal ventricular tachycardias, including torsades de pointes. As part of the post-marketing commitment, a thorough QT/QTc study will be conducted according to ICH guidelines.

Key facts

Study ID

NCT00789568

Run by

BioMarin Pharmaceutical

People needed

56

Starts

2008-10-01

Expected to finish

2009-10-01

Last updated by the study team

2021-07-23

Who can join

Age: 18 and older, up to 50. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Willing and able to provide written, signed informed consent, after the nature of the study has been explained, and prior to any research-related procedures.
• Sexually active subjects must be willing to use an acceptable method of contraception (double barrier) while participating in the study from screening onwards and for at least 4 weeks after the last dose of study drug.
• Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.
• Willing and able to comply with all study procedures.
• Healthy male and female subjects between 18 and 50 years of age, inclusive.
• Body mass index (BMI) of ≥ 18 to < 30 kg/m2 inclusive.
• Blood pressure in the range of 90 140 mmHg systolic and 50 90 mmHg diastolic at Screening and Check-in. Blood pressures can be repeated up to three times within 10 minutes of initial assessment while remaining in the supine position.
• No clinically significant 12-lead ECG abnormalities; and a QTc interval < 450 ms for males and < 470 ms for females and a resting heart rate between 45 90 beats/minute at Screening and Check-in.

You may not qualify if…

• Has known hypersensitivity to sapropterin or its excipients, or moxifloxacin.
• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
• Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• Concurrent disease or condition that would interfere with study participation or safety or any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study.
• History of clinically significant cardiac condition, eg, myocardial ischemia (including angina) or infarction, congestive heart failure, left ventricular hypertrophy, or cardiomyopathy.
• Screening, Check-in, or Baseline ECG shows any of the following:
• Sinus arrhythmia with unacceptable rate variation as judged by the Investigator.
• Excessive heart rate variation at rest, in the Investigator's opinion.
• PR interval > 210 ms.
• QRS interval > 110 ms.
• QRS and/or T wave that the Investigator judges to be unfavorable for consistently accurate QT measurements (eg, indistinct QRS onset, low amplitude T wave, inverted or terminally inverted T wave, merged T and U waves, or indistinct T offset, prominent U-wave that affects QT measurement).
• Neuromuscular artifact that cannot be readily eliminated.
• Documented history of arrhythmias (eg, ventricular arrhythmias and atrial fibrillation).
• Clinically significant electrolyte disturbances at Screening or Check-in (eg, hypo or hyperkalemia or hypocalcemia) or any condition that could lead to electrolyte disturbances (eg, eating disorder), in the Investigator's opinion.
• History of palpitations, seizures, unexplained syncopal episodes, or symptomatic arrhythmias.
• History of additional risk factors for torsade de pointes (eg, history of near-drowning survival due to loss of consciousness, family history of long QT syndrome, or family history of unexplained early sudden death).
• Any condition that, in the opinion of the Investigator, may compromise absorption, metabolism, or elimination of moxifloxacin.
• History of cancer within the last five years, with the exception of adequately treated basal cell carcinoma.
• Known allergy or intolerance to any compound in the test products or any other closely related compound, such as any member of the quinolone class of antimicrobial agents.
• Unresolved clinically significant laboratory findings, in the Investigator's opinion.
• Positive antibody screen for HBsAg, hepatitic C virus (HCV), or human immunodeficiency virus (HIV).
• Acute illness or febrile event within 72 hours of Check-in.
• Use of tobacco or nicotine-containing products within the last 30 days or have a positive urine test for cotinine prior to Check-in.
• History of alcohol or drug abuse (according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV] criteria) within 12 months prior to Check-in or have a positive urine test for alcohol or substances of abuse at Screening or Check-in.
• Use of alcoholic beverages, caffeine, and grapefruit-containing products 72 hours prior to dosing and until completion of study.

Where it is running

• PRACS Institute, Ltd. — Fargo, North Dakota, United States

Full record on ClinicalTrials.gov

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