Symptomatic Neurogenic Orthostatic HypotensionPhase 1NCT01149629
Study of the Fed-Fast Pharmocokinetics and Bioequivalance of 300mg Capsules of Droxidopa
A Phase 1 study testing Droxidopa in people with Symptomatic Neurogenic Orthostatic Hypotension, run by Chelsea Therapeutics at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Symptomatic Neurogenic Orthostatic Hypotension
- What is being tested?
- Droxidopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Aug 2010
- 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 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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.
- Male or female ≥65 years of age.
- Body mass index (BMI) between 18 and 35 kg/m2, inclusive.
- 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.
- Ability and willingness to abstain from alcohol from 48 h prior to the first dose until the completion of the study.
- 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).
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- Computerized, 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations, as judged by the investigator.
- 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.
- Nonsmoking or have quit smoking at least 6 months prior to dosing.
Who cannot join
- 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).
- Presence of an active malignancy of any type other than nonmelanomatous skin malignancies.
- History of relevant drug and/or food allergies.
- Recent history (past 5 years) of alcohol abuse or drug addiction.
- 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.
- Participation in an investigational drug study within 30 days prior to study drug administration.
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- 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.
- Positive screen for drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines) or alcohol.
- Positive screen for urine cotinine.
- Positive screen for hepatitis B surface antigen.
- Positive screen for antibodies to hepatitis C virus.
- Positive screen for antibodies to human immunodeficiency virus (HIV-1/HIV-2).
- Acute illness within 5 days prior to drug administration.
- History of coagulation disorder, thrombocytopenia, bleeding tendency, or gastrointestinal bleeding.
- Professional or ancillary personnel involved in the study.
- In the opinion of the investigator, not suitable for entry into the study.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- Droxidopa
- Keywords
- Droxidopa, Randomized, Crossover, Open Label, Bioequivalence, Fed Fast, TID
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
One capsule containing 300 mg droxidopa, given once
DroxidopaDrug
3 capsules each containing 100 mg droxidopa, give 3 times at 4 hour intervals
DroxidopaDrug
3 capsules each containing 100 mg droxidopa, given once
| Study group | Role | What they receive |
|---|---|---|
| Fed Dosing | Active comparator | Subjects fed a high calorie, high fat meal prior to receiving 3 x 100mg capsules Receives: Drug: Droxidopa |
| Fasted Dosing | Active comparator | Subjects fasted prior to receiving 3 x 100mg capsules Receives: Drug: Droxidopa |
| Bioequivalence | Active comparator | Subjects fasted prior to receiving 1x 300mg capsule Receives: Drug: Droxidopa |
| TID Dosing | Active comparator | Droxidopa 300 mg given TID Receives: Drug: Droxidopa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Droxidopa Pharmacokinetics
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.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2010 (estimated)
- Study startJul 2010
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Symptomatic Neurogenic Orthostatic HypotensionStudies of the same condition, open and under way.
- 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
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chelsea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gregory M Haugen, M.D., Principal investigator, Cetero Research, San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01149629
- Sponsor's protocol ID
- Droxidopa NOH101
- Status last verified
- Mar 2013
- First submitted
- 22 Jun 2010
- Last updated
- 20 Mar 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Chen JJ, Hewitt LA. Comparison of the Pharmacokinetics of Droxidopa After Dosing in the Fed Versus Fasted State and with 3-Times-Daily Dosing in Healthy Elderly Subjects. Drugs R D. 2018 Mar;18(1):77-86. doi: 10.1007/s40268-018-0226-z.
PubMed 29392574
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01149629
- Acronym / sponsor ID
- Droxidopa NOH101
- Keywords
- Droxidopa, Randomized, Crossover, Open Label, Bioequivalence, Fed Fast, TID
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Chelsea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jul 2010
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 23 Jun 2010 (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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Fed Dosing | Active comparator | Drug: DroxidopaSubjects fed a high calorie, high fat meal prior to receiving 3 x 100mg capsules |
| Fasted Dosing | Active comparator | Drug: DroxidopaSubjects fasted prior to receiving 3 x 100mg capsules |
| Bioequivalence | Active comparator | Drug: DroxidopaSubjects fasted prior to receiving 1x 300mg capsule |
| TID Dosing | Active comparator | Drug: DroxidopaDroxidopa 300 mg given TID |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (9 listed)
- 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.
- Male or female ≥65 years of age.
- Body mass index (BMI) between 18 and 35 kg/m2, inclusive.
- 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.
- Ability and willingness to abstain from alcohol from 48 h prior to the first dose until the completion of the study.
Key exclusion criteria (16 listed)
- 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).
- Presence of an active malignancy of any type other than nonmelanomatous skin malignancies.
- History of relevant drug and/or food allergies.
- Recent history (past 5 years) of alcohol abuse or drug addiction.
- 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.
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 |
|---|---|---|
| DroxidopaOne capsule containing 300 mg droxidopa, given once | Drug | Bioequivalence |
| Droxidopa3 capsules each containing 100 mg droxidopa, give 3 times at 4 hour intervals | Drug | TID Dosing |
| Droxidopa3 capsules each containing 100 mg droxidopa, given once | Drug | Fasted Dosing, Fed Dosing |
Primary outcome
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.
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 20 Mar 2013.
- Derived from this study: PubMed 29392574Chen JJ, Hewitt LA. Comparison of the Pharmacokinetics of Droxidopa After Dosing in the Fed Versus Fasted State and with 3-Times-Daily Dosing in Healthy Elderly Subjects. Drugs R D. 2018 Mar;18(1):77-86. doi: 10.1007/s40268-018-0226-z.
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Symptomatic Neurogenic Orthostatic Hypotension, MSA - Multiple System Atrophy
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.
Gregory M Haugen, M.D. principal investigator
Cetero Research, San Antonio
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 Droxidopa in people with Symptomatic Neurogenic Orthostatic Hypotension, run by Chelsea Therapeutics 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 9 inclusion and 16 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 20 Mar 2013. 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. 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?
Droxidopa Pharmacokinetics (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01149629, which also lists 1 linked publication.
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 20 Mar 2013.