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

March 18, 2013 updated by: Chelsea Therapeutics

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • North Dakota
      • Fargo, North Dakota, United States, 58104
        • Cetero Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

63 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Fed Dosing
Subjects fed a high calorie, high fat meal prior to receiving 3 x 100mg capsules
One capsule containing 300 mg droxidopa, given once
3 capsules each containing 100 mg droxidopa, give 3 times at 4 hour intervals
3 capsules each containing 100 mg droxidopa, given once
Active Comparator: Fasted Dosing
Subjects fasted prior to receiving 3 x 100mg capsules
One capsule containing 300 mg droxidopa, given once
3 capsules each containing 100 mg droxidopa, give 3 times at 4 hour intervals
3 capsules each containing 100 mg droxidopa, given once
Active Comparator: Bioequivalence
Subjects fasted prior to receiving 1x 300mg capsule
One capsule containing 300 mg droxidopa, given once
3 capsules each containing 100 mg droxidopa, give 3 times at 4 hour intervals
3 capsules each containing 100 mg droxidopa, given once
Active Comparator: TID Dosing
Droxidopa 300 mg given TID
One capsule containing 300 mg droxidopa, given once
3 capsules each containing 100 mg droxidopa, give 3 times at 4 hour intervals
3 capsules each containing 100 mg droxidopa, given once

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Droxidopa Pharmacokinetics
Time Frame: 24 hours
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.
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Gregory M Haugen, M.D., Cetero Research, San Antonio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (Actual)

August 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

June 22, 2010

First Submitted That Met QC Criteria

June 22, 2010

First Posted (Estimate)

June 23, 2010

Study Record Updates

Last Update Posted (Estimate)

March 20, 2013

Last Update Submitted That Met QC Criteria

March 18, 2013

Last Verified

March 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Symptomatic Neurogenic Orthostatic Hypotension

Clinical Trials on Droxidopa

3
Subscribe