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

NCT01327066 | Completed Phase 1

• 1 other identifier: Droxidopa QTc102
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

QTc Interval

Keywords

QTc; ECG Effects

Outcome Measures

Primary Outcomes (1)

• ECG Effects

  The primary ECG endpoint is the time matched, placebo adjusted change from Baseline in QT interval corrected using an individual correction method (QTcI) (ΔΔQTcI). The QTcI method provides an optimization of QT correction for HR as compared with fixed exponent approaches such as Bazett (QTcB) or Fridericia (QTcF).

  Baseline to End of Treatment (12 days)

Secondary Outcomes (1)

• QTcF and QTcB (for historic reasons only), HR, and PR, QRS, and uncorrected QT intervals, change in ECG morphological patterns, and the correlation between the QTcI change and droxidopa plasma concentrations

  Baseline to End of Treatment (12 days)

Study Arms (4)

Droxidopa - Therapeutic

EXPERIMENTAL

Droxidopa 600 mg

Drug: Droxidopa

Droxidopa - Supratherapeutic Dose

EXPERIMENTAL

Droxidopa 2000 mg

Drug: Droxidopa

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Moxifloxacin; Drug: Placebo

Moxifloxacin

ACTIVE COMPARATOR

Moxifloxacin 400 mg dose

Drug: Moxifloxacin

Interventions

Droxidopa DRUG

600 mg, single oral dose

Also known as: L-DOPS, Northera

Droxidopa - Therapeutic

Moxifloxacin DRUG

400 mg, single oral dose

Also known as: Avelox

Moxifloxacin; Placebo

Placebo DRUG

Placebo matching Droxidopa or Moxifloxacin

Also known as: sugar pill, sham

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subject in good general health and 18 to 45 years of age, inclusive.
• 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.
• Subject has a body mass index of 18.0 to 30.0 kg/m2, inclusive.
• Subject provides written informed consent.
• Subject is willing and able to comply with all study requirements.
• 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.

You may not qualify if:

• 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.
• 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).
• 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.
• Subject has a history of drug or alcohol abuse or dependence within 1 year before Check in.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Subject consumes ≥ 500 mg per day of caffeine (eg, 5 cups of tea or coffee; 8 cans or five 20 ounce bottles of cola).
• Subject has been treated with any investigational agent within 30 days before Check in (or 5 half-lives of the compound, if longer).
• 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.
• 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).

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

Droxidopa; Moxifloxacin; Sugars; salicylhydroxamic acid

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Thomas Hunt, MD

  PPD Phase I Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 1, 2011
• Study Start: March 1, 2011
• Primary Completion: April 1, 2011
• Study Completion: June 1, 2011
• Last Updated: March 7, 2012

Record last verified: 2012-03

Locations

US (1)