Electrocardiographic (ECG) Safety Study of Droxidopa at Clinical and Supratherapeutic Dose

• Status: Completed
• Trial end date: 2011-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is define the electrocardiographic (ECG) effects of Droxidopa at clinical (600 mg) and supratherapeutic (2000 mg) doses compared with placebo and moxifloxacin in healthy male and female subjects.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Chelsea Therapeutics
• Treatments: Droxidopa; Fluoroquinolones; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination

Criteria

Inclusion Criteria:

1. Male or female subject in good general health and 18 to 45 years of age, inclusive.

2. Female subjects must be nonpregnant, nonlactating, and have a negative serum pregnancy test before enrollment in the study. Female subjects of childbearing potential (including perimenopausal women who have had menstrual bleeding within 1 year) must be using appropriate birth control (abstinence and/or barrier methods and/or oral, injectable, or implantable hormonal contraceptives) during the entire duration of the study. Women are considered of non-childbearing potential if they are menopausal (last menstrual period greater than 12 months before Check in and a serum follicle stimulating hormone level greater than 40 mIU/mL) or have been surgically sterilized (documented hysterectomy, tubal ligation, or bilateral oophorectomy) at least 6 weeks before Check in.

3. Subject has a body mass index of 18.0 to 30.0 kg/m2, inclusive.

4. Subject provides written informed consent.

5. Subject is willing and able to comply with all study requirements.

6. Subject has no clinically significant abnormal medical history, clinical laboratory results, vital sign measurements, 12 lead safety ECG results, or physical examination findings during Screening.

Exclusion Criteria:

1. Subject is currently participating in another clinical study of an investigational drug (or a medical device), or has participated in a study of this type within 30 days before Check in.

2. Subject has a history or current evidence of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at the time of dosing or mild allergic reactions to drugs other than those listed in exclusion criterion #16), hematologic, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic disease. Exceptions to these criteria (eg, stable mild joint disease, cholecystectomy, or childhood asthma) may be made after discussion with the medical monitor.

3. Subject has used any prescribed or over the counter medication without the approval of the investigator or sponsor within 1 week before the first dose of study drug (including dietary supplements, herbal remedies, and medications known to prolong the QT/corrected QT [QTc] interval).

4. Subject is receiving any anticoagulant (eg, coumadin, heparin, low molecular weight heparin) or has received any anticoagulant within 3 months before Check in. Subjects who are receiving any drugs that affect platelet function (eg, aspirin, including low-dose aspirin) will also be excluded.

5. Subject has a history of drug or alcohol abuse or dependence within 1 year before Check in.

6. Subject has donated blood or blood components within 4 weeks before Check in. The investigator should instruct subjects who participate in this study not to donate blood or blood components for 4 weeks after completion of the study.

7. Subject has a sustained supine systolic blood pressure > 140 mm Hg or < 90 mm Hg or a supine diastolic blood pressure > 95 mm Hg or < 50 mm Hg at Screening or Check in. Blood pressure may be retested once in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic pressure values are outside the stated limits after 2 assessments, and the subject may not be randomized.

8. Subject has a resting heart rate (HR) of < 45 beats per minute or > 100 beats per minute when vital signs are measured at Screening or Check in.

9. Subject has an abnormal screening ECG indicating a second or third degree atrioventricular block, or one or more of the following: QRS interval > 110 milliseconds (ms); QT interval corrected for HR by Fridericia's formula (QTcF) > 450 ms; PR interval > 200 ms; or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant.

10. Subject has a history of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia. Subjects will also be excluded if there is a family history of long QT syndrome or Brugada syndrome.

11. Subject uses or has used nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff) within 2 weeks before Check in, or subject has a positive cotinine result (indicating active current smoking) at Screening or Check in.

12. Subject has consumed alcohol or xanthine-containing products (eg, tea, coffee, chocolate, cola) within 72 hours before Check in, or subject has a positive result for drug(s) of abuse or ethanol at Screening or Check in.

13. Subject consumes ≥ 500 mg per day of caffeine (eg, 5 cups of tea or coffee; 8 cans or five 20 ounce bottles of cola).

14. Subject has been treated with any investigational agent within 30 days before Check in (or 5 half-lives of the compound, if longer).

15. Subject who, for any reason, is deemed by the investigator to be inappropriate for this study, including a subject who is unable to communicate or cooperate with the investigator.

16. Subject has known allergies to droxidopa, moxifloxacin, any excipient in the study drug(s), or encapsulation formulations (subject will not be excluded for mild allergic reactions to drugs other than those listed in this criterion).

17. Subject has received treatment with droxidopa within 30 days before Check in.