Study of the Fed-Fast Pharmocokinetics and Bioequivalance of 300mg Capsules of Droxidopa

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chelsea Therapeutics
ClinicalTrials.gov Identifier:
NCT01149629
First received: June 22, 2010
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

One purpose of this study is to determine if taking droxidopa after eating will have an effect on how the body processes (absorbs and eliminates) the drug in healthy elderly subjects. Another purpose of this study is to see how the body processes (absorbs and eliminates) one 300mg capsule compared to three 100mg capsules. This study will also evaluate how well the body processes (absorbs and eliminates) and tolerates droxidopa when a 300 mg capsule is given 3 times a day for a total dose of 900 mg over the course of one day.

Droxidopa is used to treat low blood pressure upon standing in patients with diseases of the nervous system, to prevent low blood pressure in patients with kidney disease during hemodialysis (removal of waste products of the blood), and to treat frozen gait (walking, stepping or running) and dizziness upon standing in patients with Parkinson's disease.


Condition Intervention Phase
Symptomatic Neurogenic Orthostatic Hypotension
Drug: Droxidopa
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Three-Period, Three-Sequence, Single-Dose Crossover and Separate Three-Daily-Dose Treatment Period Study Comparing the Pharmacokinetic Profiles Following Oral Dosing of 300 mg of Droxidopa in the Fed Versus Fasted State, the Bioequivalence of Three 100 mg Capsules of Droxidopa Versus a Single 300 mg Capsule of Droxidopa, and 300 mg of Droxidopa Given Three Times at Four Hour Intervals in Healthy, Elderly Subjects

Resource links provided by NLM:


Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • Droxidopa Pharmacokinetics [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples will be collected at the time from 0 to 24 hours. Cmax, Tmax, AUC(0-∞), AUC(0-t), t1/2, and CL/F, will be determined for plasma concentrations of droxidopa in Parts I and II and will also be determined for two of its metabolites (3-OM-droxidopa and norepinephrine) in Part II only.


Estimated Enrollment: 24
Study Start Date: July 2010
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fed Dosing
Subjects fed a high calorie, high fat meal prior to receiving 3 x 100mg capsules
Drug: Droxidopa
3 capsules each containing 100 mg droxidopa, given once
Active Comparator: Fasted Dosing
Subjects fasted prior to receiving 3 x 100mg capsules
Drug: Droxidopa
3 capsules each containing 100 mg droxidopa, given once
Active Comparator: Bioequivalence
Subjects fasted prior to receiving 1x 300mg capsule
Drug: Droxidopa
One capsule containing 300 mg droxidopa, given once
Active Comparator: TID Dosing
Droxidopa 300 mg given TID
Drug: Droxidopa
3 capsules each containing 100 mg droxidopa, give 3 times at 4 hour intervals

Detailed Description:

This is a two-part study. Part I is a randomized, open-label, three-period crossover study in 24 healthy, elderly, male or female subjects. Subjects will be allocated to one of three treatment sequences according to a randomization schedule prepared prior to the start of the study. Each subject will receive a single, oral dose of three 100 mg capsules of droxidopa with 240 mL of water either in the fasted state (Treatment A) or immediately following the consumption of a standardized high-fat meal (Treatment B) and a single, oral dose of one 300 mg capsule of droxidopa with 240 mL of water in the fasted state (Treatment C) on Days 1, 4, and 7. Subjects will be discharged from the research clinic on Day 8 after completing all posttreatment follow-up assessments and will return to the research clinic approximately 1 week later for Part II of the study. Part II of the study is an open-label design where all subjects will receive three doses of 300 mg droxidopa (three 100 mg capsules/dose) at 4 hour intervals and will be followed for a concurrent 24 h period.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Provide written consent on an IRB-approved Informed Consent Form (ICF), prior to any study-specific evaluation. Subjects should have the ability to read and understand the ICF, ask for any clarifications from the study staff, and be able to comply with all planned study procedures.
  2. Male or female ≥65 years of age.
  3. Body mass index (BMI) between 18 and 35 kg/m2, inclusive.
  4. If female, not pregnant (or lactating), as evidenced by a negative serum pregnancy test, and is surgically sterile (hysterectomy, bilateral ovariectomy, or bilateral tubal ligation), or at least 2 years postmenopausal.
  5. Ability and willingness to abstain from alcohol from 48 h prior to the first dose until the completion of the study.
  6. No clinically significant abnormalities on the basis of medical history, physical examination, and vital signs unless currently controlled with medical treatment (e.g., a stable medication dosing regimen).
  7. Computerized, 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations, as judged by the investigator.
  8. All values for hematology, clinical chemistry, and urinalysis are normal or if abnormal—are deemed not clinically significant as judged by a physician investigator with documented agreement from the Medical Monitor.
  9. Nonsmoking or have quit smoking at least 6 months prior to dosing.

Exclusion Criteria:

  1. Presence of active or recurring clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease not currently controlled with medical treatment (e.g., a stable medication dosing regimen).
  2. Presence of an active malignancy of any type other than nonmelanomatous skin malignancies.
  3. History of relevant drug and/or food allergies.
  4. Recent history (past 5 years) of alcohol abuse or drug addiction.
  5. Required use of concomitant medications that could confound the PK or safety evaluation, such as medications that affect GI function (including proton pump inhibitors or metoclopramide) or vasoconstricting agents (e.g., ephedrine, dihydroergotamine, or midodrine), -triptans (e.g., sumatriptan, naratriptan, zolmitriptan, rizatriptan), halogen-containing anesthetics (e.g., cyclopropane, or halothane), catecholaminecontaining preparations (e.g., isoprenaline), non-selective MAOIs, ergotamine derivatives (except for anti-Parkinson medications), or any drugs with anti-hypertensive properties that in the investigator's opinion, could significantly contribute to the subject's orthostatic hypotension.
  6. Participation in an investigational drug study within 30 days prior to study drug administration.
  7. Donated a unit of blood (500 mL) or plasma within the 30-day period prior to the initial dose of study medication or who intend to donate blood or plasma within a 30-day period following the final dose of study medication.
  8. Positive screen for drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines) or alcohol.
  9. Positive screen for urine cotinine.
  10. Positive screen for hepatitis B surface antigen.
  11. Positive screen for antibodies to hepatitis C virus.
  12. Positive screen for antibodies to human immunodeficiency virus (HIV-1/HIV-2).
  13. Acute illness within 5 days prior to drug administration.
  14. History of coagulation disorder, thrombocytopenia, bleeding tendency, or gastrointestinal bleeding.
  15. Professional or ancillary personnel involved in the study.
  16. In the opinion of the investigator, not suitable for entry into the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01149629

Locations
United States, North Dakota
Cetero Research
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
Chelsea Therapeutics
Investigators
Principal Investigator: Gregory M Haugen, M.D. Cetero Research, San Antonio
  More Information

No publications provided

Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT01149629     History of Changes
Other Study ID Numbers: Droxidopa NOH101
Study First Received: June 22, 2010
Last Updated: March 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Chelsea Therapeutics:
Droxidopa
Randomized
Crossover
Open Label
Bioequivalence
Fed Fast
TID

Additional relevant MeSH terms:
Hypotension
Hypotension, Orthostatic
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Droxidopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014