DyskinesiasPhase 2NCT04912115
Randomized, Double-Blind, Active Placebo-Controlled Study of Ketamine to Treat Levodopa-Induced Dyskinesia
A Phase 2 study testing Ketamine and Midazolam in people with Dyskinesias and Movement Disorders, run by PharmaTher Inc. at 7 sites in United States.
Trial summary
A Multi-Center, Phase II, Randomized, Double-Blind, Prospective, Active Placebo-Controlled Trial of Sub-Anesthetic Intravenous Infusion of Ketamine to Treat Levodopa-Induced Dyskinesia in Subjects with Parkinson's Disease. Read more about this study
- Who is it for?
- Ages 30 to 85 years
- Conditions the study is for
- Dyskinesias, Movement Disorders, Central Nervous System Diseases
- What is being tested?
- Ketamine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 7 sitesUnited States
- Study dates
- 5 Oct 2021to 30 Mar 2024
- Phase
- Phase 2
- 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 30 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with Parkinson's Disease as defined by the UK Parkinson's Disease Society Brain Bank Criteria
- Signed a current IEC approved informed consent form
- Male or female patients between ages 30-85 years
- At least three years of prior treatment with levodopa of at least 400 mg daily subject to a maximum of 8 divided doses per day (excluding bedtime and nighttime)
- Waking day dyskinesia of > 25% determined as a score of ≥2 as per Question 4.1 on the UPDRS
- Ambulatory or ambulatory-aided (e.g., walker or cane) and able to complete study assessments
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- Have been on stable doses of all anti-Parkinson's medications for 30 days prior to entry into the study, including a levodopa preparation administered not less than three times daily, and be willing to remain on the same doses of medications throughout the course of the study
- Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and the patient must be willing to continue the same doses and regimens during study participation.
- The subject/caregiver must demonstrate the ability to complete an accurate home diary based on training and evaluation (visit 2)
- Subjects must have available a responsible adult caregiver/companion who will drive the subject home following infusions
- Female subjects not of childbearing potential
- Male subjects, regardless of their fertility status, with nonpregnant women of childbearing potential (WOCBP) partners must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use a highly effective (less than 1% failure rate) method of contraception (such as combination oral contraceptives, implanted contraceptives, or intrauterine devices) or effective method of contraception (such as diaphragms with spermicide or cervical sponges) for the duration of the study and until their plasma concentrations are below the level that could result in a relevant potential exposure to a possible fetus, predicted to be 90 days following the last dose of study drug
Who cannot join
- Diagnosis of an atypical or secondary Parkinsonian syndrome
- Lack of documented response to levodopa
- Hoehn and Yahr stage of 5
- Known prior exposure to ketamine or other NMDA inhibitors within the last 30 days
- History of neurosurgical intervention related to PD (e.g., deep brain stimulation)
- History of seizures within two years prior to screening
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- History of transient ischemic attacks or stroke within two years prior to screening
- History of intracerebral hemorrhage due to hypertension.
- History of clinically significant arrhythmia or unstable angina within the past five years
- History of myocardial infarction within 2 years prior to screening
- History of NYHA Class 3 or 4 heart failure within 2 years prior to screening
- Aneurysmal vascular disease (e.g., intracranial, thoracic or abdominal aorta)
- History of hypertensive encephalopathy
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Investigative Site #2
Chula Vista, California, 91910
Investigative Site #1
Fountain Valley, California, 92708
Investigative Site #3
Miami, Florida, 33032
Investigative Site #6
Miami, Florida, 33175
Investigative Site #4
Plymouth, Michigan, 48170
Investigative Site #5
Rolling Meadows, Illinois, 60008
Investigative Site #7
Tucson, Arizona, 85719
About this study
Official title: A Multi-Center, Phase II, Randomized, Double-Blind, Prospective, Active Placebo- Controlled Trial of Sub-Anesthetic Intravenous Infusion of Ketamine to Treat Levodopa- Induced Dyskinesia in Subjects With Parkinson's Disease
A Multi-Center, Phase II, Randomized, Double-Blind, Prospective, Active Placebo-Controlled Trial of Sub-Anesthetic Intravenous Infusion of Ketamine to Treat Levodopa-Induced Dyskinesia in Subjects with Parkinson's Disease.
Read the detailed description
This Phase II trial is a prospective, double-blind, randomized, parallel trial-design with two arms. Subjects will be randomized to treatment with the investigational product (ketamine) or an active control (midazolam). The active control causes mild sedation and is employed to minimize unmasking of the test article.
The study is an out-patient study. However, infusion days and days involving prolonged assessments are expected to require the subject to be onsite. Subjects will return to the site for safety and efficacy evaluations. On Day 1, PK samples will be collected near the end of Infusion 1 and post-infusion to evaluate near-steady-state blood levels in all subjects. Intensive PK sampling will be conducted in all subjects prior to, during, and a few hours after Infusion 2 (Day 5 ± 2).
The primary objective of the study is to evaluate the effects of low-dose intravenous infusion of ketamine on levodopa-induced dyskinesia (LID) in patients with Parkinson's disease. All patients included in the study should meet the inclusion criteria. Half of the participants will receive ketamine, while the other half will receive active placebo (Midazolam). All participants will be assigned to either the active group or the control group randomly. During the clinical trial, both investigators and patients are double-blind except serious adverse events occurred.
- Conditions
- Dyskinesias, Movement Disorders, Central Nervous System Diseases, Nervous System Diseases, Neurologic Manifestations
- Medical subject headings
- Dyskinesias, Movement Disorders, Central Nervous System Diseases, Nervous System Diseases, Neurologic Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Ketamine is an FDA-approved N-methyl-D-aspartate (NMDA) receptor-modulating drug pharmacologically classified as an NMDA receptor antagonist (also noted to be a weak opioid receptor agonist).
MidazolamDrug
Midazolam is a benzodiazepine used for anesthesia, procedural sedation, trouble sleeping, and severe agitation.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Ketamine will be administered as intravenous infusions with infusion rates ranging from 0.1 mg/kg/hr to 0.30 mg/kg/hr. To maintain blinding, both active and placebo will be infused at similar infusion rates (mL/hr). Receives: Drug: Ketamine |
| Midazolam | Active comparator | Midazolam will be administered as intravenous infusions with infusion rates ranging from 0.009 mg/kg/hr to 0.027 mg/kg/hr. To maintain blinding, both active and placebo will be infused at similar infusion rates (mL/hr). Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Unified Dyskinesia Rating Scale (UDysRS) total score from Baseline to Week 8.
The change from baseline to week 8 of treatment in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS). The Unified Dyskinesia Rating Scale (UDysRS) is administered to assess dyskinesia. The scoring range is 0-104, where higher score means more dyskinesia.
Measured: 8 weeks
Secondary outcomes (2)
Change in total daily OFF times as assessed by subject completed 24-hour diaries, from Baseline to Week 8.
Change in daily "OFF"-time as assessed with patient diaries from run-in to week 8. This is a self administered diary where patients assess their motor state every half hour during 24 hours.
Measured: 8 weeks
Change in the UPDRS total score of part III (motor) and sum score of Questions 4.1 and 4.2 (dyskinesia) in part IV from Baseline to Week 8.
Change in MDS-UPDRS sum score of part III (Motor Examination) from baseline to week 8. Minimum value is 0 and maximum value is 124. Higher score mean a worse outcome.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2021
- Study start5 Oct 2021
- Primary completion30 Dec 2023 (estimated)
- Study completion30 Mar 2024 (estimated)
Why it stopped: Seeking Pivotal study initiation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DyskinesiasStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaTher Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, PharmaTher Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04912115
- Sponsor's protocol ID
- KET-001
- Status last verified
- Nov 2023
- First submitted
- 25 May 2021
- Last updated
- 18 Nov 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Phase II, Randomized, Double-Blind, Prospective, Active Placebo- Controlled Trial of Sub-Anesthetic Intravenous Infusion of Ketamine to Treat Levodopa- Induced Dyskinesia in Subjects With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT04912115
- Acronym / sponsor ID
- KET-001
- Conditions
- Dyskinesias, Movement Disorders, Central Nervous System Diseases, Nervous System Diseases, Neurologic Manifestations
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Seeking Pivotal study initiation
- Enrolment
- 30 participants (actual)
- Lead sponsor
- PharmaTher Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Oct 2021 (actual)
- Primary completion
- 30 Dec 2023 (estimated)
- Study completion
- 30 Mar 2024 (estimated)
- First posted
- 3 Jun 2021 (actual)
- 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.
A Multi-Center, Phase II, Randomized, Double-Blind, Prospective, Active Placebo-Controlled Trial of Sub-Anesthetic Intravenous Infusion of Ketamine to Treat Levodopa-Induced Dyskinesia in Subjects with Parkinson's Disease.
Detailed description
This Phase II trial is a prospective, double-blind, randomized, parallel trial-design with two arms. Subjects will be randomized to treatment with the investigational product (ketamine) or an active control (midazolam). The active control causes mild sedation and is employed to minimize unmasking of the test article.
The study is an out-patient study. However, infusion days and days involving prolonged assessments are expected to require the subject to be onsite. Subjects will return to the site for safety and efficacy evaluations. On Day 1, PK samples will be collected near the end of Infusion 1 and post-infusion to evaluate near-steady-state blood levels in all subjects. Intensive PK sampling will be conducted in all subjects prior to, during, and a few hours after Infusion 2 (Day 5 ± 2).
The primary objective of the study is to evaluate the effects of low-dose intravenous infusion of ketamine on levodopa-induced dyskinesia (LID) in patients with Parkinson's disease. All patients included in the study should meet the inclusion criteria. Half of the participants will receive ketamine, while the other half will receive active placebo (Midazolam). All participants will be assigned to either the active group or the control group randomly. During the clinical trial, both investigators and patients are double-blind except serious adverse events occurred.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineKetamine will be administered as intravenous infusions with infusion rates ranging from 0.1 mg/kg/hr to 0.30 mg/kg/hr. To maintain blinding, both active and placebo will be infused at similar infusion rates (mL/hr). |
| Midazolam | Active comparator | Drug: MidazolamMidazolam will be administered as intravenous infusions with infusion rates ranging from 0.009 mg/kg/hr to 0.027 mg/kg/hr. To maintain blinding, both active and placebo will be infused at similar infusion rates (mL/hr). |
Who may qualify
- Ages
- 30 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients diagnosed with Parkinson's Disease as defined by the UK Parkinson's Disease Society Brain Bank Criteria
- Signed a current IEC approved informed consent form
- Male or female patients between ages 30-85 years
- At least three years of prior treatment with levodopa of at least 400 mg daily subject to a maximum of 8 divided doses per day (excluding bedtime and nighttime)
- Waking day dyskinesia of > 25% determined as a score of ≥2 as per Question 4.1 on the UPDRS
Key exclusion criteria (13 listed)
- Diagnosis of an atypical or secondary Parkinsonian syndrome
- Lack of documented response to levodopa
- Hoehn and Yahr stage of 5
- Known prior exposure to ketamine or other NMDA inhibitors within the last 30 days
- History of neurosurgical intervention related to PD (e.g., deep brain stimulation)
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 |
|---|---|---|
| KetamineKetamine is an FDA-approved N-methyl-D-aspartate (NMDA) receptor-modulating drug pharmacologically classified as an NMDA receptor antagonist (also noted to be a weak opioid receptor agonist). | Drug | Ketamine |
| MidazolamMidazolam is a benzodiazepine used for anesthesia, procedural sedation, trouble sleeping, and severe agitation. | Drug | Midazolam |
Primary outcome
Change in the Unified Dyskinesia Rating Scale (UDysRS) total score from Baseline to Week 8.
Time frame: 8 weeks
The change from baseline to week 8 of treatment in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS). The Unified Dyskinesia Rating Scale (UDysRS) is administered to assess dyskinesia. The scoring range is 0-104, where higher score means more dyskinesia.
2 secondary outcomes
Change in total daily OFF times as assessed by subject completed 24-hour diaries, from Baseline to Week 8.
Time frame: 8 weeks
Change in the UPDRS total score of part III (motor) and sum score of Questions 4.1 and 4.2 (dyskinesia) in part IV from Baseline to Week 8.
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
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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.
Study Director study director
PharmaTher Inc.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine and Midazolam in people with Dyskinesias and Movement Disorders, run by PharmaTher Inc. at 7 sites 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 12 inclusion and 13 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: paused, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Change in the Unified Dyskinesia Rating Scale (UDysRS) total score from Baseline to Week 8. (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Nov 2023; AzTrials last refreshed its copy on 3 Nov 2026.