PhenylketonuriaPhase 1NCT00789568
A Phase 1 Study to Evaluate Effects of Sapropterin Dihydrochloride on QTc Intervals in Healthy Adult Subjects
A Phase 1 study testing sapropterin dihydrochloride and Moxifloxacin in people with Phenylketonuria, run by BioMarin Pharmaceutical at 1 site in United States.
Trial summary
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®). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- sapropterin dihydrochloride and Moxifloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Oct 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 35Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Placebo- and Active-controlled Crossover Study to Evaluate the Effects of Sapropterin Dihydrochloride Oral Administration on QTc Intervals in Healthy Adult Subjects
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.
- Conditions
- Phenylketonuria
- Being tested
- sapropterin dihydrochloride, Moxifloxacin, Moxifloxacin placebo
- Keywords
- Hyperphenylalanemia due to Phenylketonuria
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapropterin dihydrochlorideDrug
Also called Kuvan
20 mg/kg and 100 mg/kg
MoxifloxacinDrug
Moxifloxacin is included as a positive control to demonstrate the assay sensitivity based on the expected increased QTc response.
Moxifloxacin placeboDrug
Moxifloxacin placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Sapropterin Dihydrochloride 100mg/kg and placebo Moxifloxacin | Experimental | A single dose of 100mg/kg of Sapropterin Dihydrochloride taken along with placebo Moxifloxacin. Receives: Drug: sapropterin dihydrochloride; Drug: Moxifloxacin placebo |
| Sapropterin Dihydrochloride 20mg/kg and placebo Moxifloxacin | Experimental | A single dose of 20mg/kg of Sapropterin Dihydrochloride taken along with a placebo Moxifloxacin. Receives: Drug: sapropterin dihydrochloride; Drug: Moxifloxacin placebo |
| Sapropterin Dihydrochloride placebo and Moxifloxacin | Active comparator | No placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with 400mg of Moxifloxacin. Receives: Drug: Moxifloxacin |
| Sapropterin Dihydrocholide placebo and Moxifloxacin placebo | Placebo comparator | No placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with placebo of Moxifloxacin. Receives: Drug: Moxifloxacin placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine if a single supratherapeutic dose of sapropterin or a single therapeutic dose of sapropterin has an effect on cardiac repolarization compared with placebo as a change from baseline measured by the subject specific QT correction formula(QTci)
Measured: Complete study
Secondary outcomes (3)
Determine if there is a pharmacodynamic relationship between the duration of the QT/QTc intervals and the plasma concentration of sapropterin
Measured: Complete Study
To obtain additional pharmacokinetic information for oral sapropterin at the proposed therapeutic and supra-therapeutic doses.
Measured: Complete Study
To generate additional safety information
Measured: Complete Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2008 (estimated)
- Study startOct 2008
- Primary completionJan 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Don Nwose, MD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00789568
- Sponsor's protocol ID
- QTC-001
- Status last verified
- Aug 2014
- First submitted
- 10 Nov 2008
- Last updated
- 23 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Placebo- and Active-controlled Crossover Study to Evaluate the Effects of Sapropterin Dihydrochloride Oral Administration on QTc Intervals in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT00789568
- Acronym / sponsor ID
- QTC-001
- Conditions
- Phenylketonuria
- Keywords
- Hyperphenylalanemia due to Phenylketonuria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 13 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sapropterin Dihydrochloride 100mg/kg and placebo Moxifloxacin | Experimental | Drug: sapropterin dihydrochloride, Drug: Moxifloxacin placeboA single dose of 100mg/kg of Sapropterin Dihydrochloride taken along with placebo Moxifloxacin. |
| Sapropterin Dihydrochloride 20mg/kg and placebo Moxifloxacin | Experimental | Drug: sapropterin dihydrochloride, Drug: Moxifloxacin placeboA single dose of 20mg/kg of Sapropterin Dihydrochloride taken along with a placebo Moxifloxacin. |
| Sapropterin Dihydrochloride placebo and Moxifloxacin | Active comparator | Drug: MoxifloxacinNo placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with 400mg of Moxifloxacin. |
| Sapropterin Dihydrocholide placebo and Moxifloxacin placebo | Placebo comparator | Drug: Moxifloxacin placeboNo placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with placebo of Moxifloxacin. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (35 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sapropterin dihydrochlorideAlso: Kuvan20 mg/kg and 100 mg/kg | Drug | Sapropterin Dihydrochloride 100mg/kg and placebo Moxifloxacin, Sapropterin Dihydrochloride 20mg/kg and placebo Moxifloxacin |
| MoxifloxacinMoxifloxacin is included as a positive control to demonstrate the assay sensitivity based on the expected increased QTc response. | Drug | Sapropterin Dihydrochloride placebo and Moxifloxacin |
| Moxifloxacin placeboMoxifloxacin placebo tablet | Drug | Sapropterin Dihydrochloride 100mg/kg and placebo Moxifloxacin, Sapropterin Dihydrochloride 20mg/kg and placebo Moxifloxacin, Sapropterin Dihydrocholide placebo and Moxifloxacin placebo |
Primary outcome
To determine if a single supratherapeutic dose of sapropterin or a single therapeutic dose of sapropterin has an effect on cardiac repolarization compared with placebo as a change from baseline measured by the subject specific QT correction formula(QTci)
Time frame: Complete study
3 secondary outcomes
Determine if there is a pharmacodynamic relationship between the duration of the QT/QTc intervals and the plasma concentration of sapropterin
Time frame: Complete Study
To obtain additional pharmacokinetic information for oral sapropterin at the proposed therapeutic and supra-therapeutic doses.
Time frame: Complete Study
To generate additional safety information
Time frame: Complete Study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Don Nwose, MD study director
BioMarin Pharmaceutical
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sapropterin dihydrochloride and Moxifloxacin in people with Phenylketonuria, run by BioMarin Pharmaceutical at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine if a single supratherapeutic dose of sapropterin or a single therapeutic dose of sapropterin has an effect on cardiac repolarization compared with placebo as a change from baseline measured by the subject specific QT correction formula(QTci) (time frame: Complete study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2021; AzTrials last refreshed its copy on 7 Nov 2026.