| Eligibility |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Subjects who have taken:
- Any prescription medications or over-the-counter medications including herbal
products (eg, St. John's Wort, milk thistle), antacids and nonsteroidal
anti-inflammatory medication for acute pain for more than 5 days within 30 days
(or 5 elimination half-lives, whichever is longer) of commencing study drug
dosing, with the exception of hormonal contraceptives (oral, implant, patch or
injections), including Depo-Provera®. For drugs with an elimination half-life
greater than 10 days, the prohibition of prior use will be extended to 60 days.
- Any planned concomitant medication while in the study, including antacids that
contain calcium, magnesium, or aluminum (eg, Rolaids or Tums), the ulcer medicine
sucralfate (Carafate), or vitamin or mineral supplements that contain calcium,
iron, or zinc from 48 hours prior to Baseline (Day -1) and until completion of
the study.
- Any psychiatric, behavioral, or neuromuscular condition that may compromise the
Investigator's evaluation of drug effect.
- History of intentional suicidal ideation, suicide attempts, depression requiring
treatment, or significant depression in the opinion of the Investigator.
- Subjects who cannot tolerate a controlled, quiet study environment, including
avoidance during specified timepoints of music, TV, movies, games, and activities that
may cause excitement, emotional tension, or arousal.
- Subjects who cannot tolerate the study-specified diet.
- Subjects who are unwilling to comply with study rules, including attempting to void at
specified times (prior to ECG timepoints) or maintain quiet, motionless supine posture
during specified timepoints.
- Rigorous exercise = 72 hours prior to Check-in or subjects who will not agree or be
able to refrain from rigorous exercise until completion of study.
- In the opinion of the Investigator, the presence of any other behavior or condition
that increases the risk to individual safety or risk of compromising study objectives.
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