Ignite Creation Date:
2024-05-06 @ 9:42 AM
Last Modification Date:
2024-10-26 @ 12:18 PM
Study NCT ID:
NCT03051256
Status:
COMPLETED
Last Update Posted:
2023-11-01
First Post:
2017-02-03
Brief Title:
Safety Tolerability PK Profile and Symptom Response of a 7-Day Dosing With 25 mg or 50 mg Daily of REL-1017 in MDD
Sponsor:
Relmada Therapeutics Inc
Organization:
Relmada Therapeutics Inc
Study Overview
Official Title:
Phase 2a Multicenter Randomized Double-Blind Placebo-Controlled Study to Assess the Safety Tolerability PK Profile and Symptom Response of a 7-Day Dosing of REL-1017 as Adjunctive Therapy in the Treatment of Pts Diagnosed With MDD
Status:
COMPLETED
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This a Phase 2a multicenter randomized double-blind placebo controlled 3 arm study to assess the safety and tolerability of multiple oral doses of REL-1017 25 mg and 50 mg as adjunctive therapy in the treatment of patients diagnosed with major depressive disorder MDD The patients will be adults with MDD who are diagnosed with a current MDE who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication This population will provide the opportunity to compare the safety and efficacy effects of treatment with an approved antidepressant in conjunction with REL-1017 versus the effects of an antidepressant alone This study includes in-patient and out-patient periods
Detailed Description:
Currently available medications have proven to be useful for the treatment of depression but also have limitations including low response rates a significant number of treatment resistant patients and time-lag for response which emphasizes a major unmet need for more efficacious and faster-acting antidepressants Recent studies have demonstrated that ketamine a non-competitive glutamate-N-methyl-D-Aspartate NMDA receptor antagonist produces rapid onset 2 hours and long-lasting 7 days antidepressant actions in treatment resistant patients This rapid action by a mechanism completely different from typical monoamine reuptake inhibitors represents a significant finding in the field of depression
Racemic methadone the 5050 combination of d-methadone and l-methadone has been in widespread use for decades and has been studied extensively Methadone is currently approved for use in the management of severe pain detoxification treatment of opioid addiction and maintenance treatment of opioid addiction
The results of a study evaluating the receptor binding profiles of racemic methadone and its stereoisomers suggest that d-methadone does not essentially contribute to the opioid effect of racemic methadone and that it has a 10 times lower affinity for the mu1 mu2 and delta opioid receptors compared to l-methadone Racemic methadone and its d- and l isomers exhibit similar affinities for the non-competitive binding site of the NMDA receptor and are non-competitive NMDA receptor antagonists
In the forced swim test a rodent behavioral model of antidepressant activity both ketamine and d-methadone at all doses tested significantly decreased the immobility of the rats compared to the vehicle suggesting antidepressant like activity Neither drug increased spontaneous locomotor activity
Relmada has conducted 2 clinical studies to identify the dose levels of REL-1017 d-methadone that have little to no opioid effects and that are expected to possess NMDA antagonistic properties for the evaluation of oral REL-1017 in the treatment of MDD and neuropathic pain conditions Initial Phase 1 single ascending dose and multiple ascending dose clinical studies of REL-1017 were designed to evaluate the safety and tolerance of the pure d methadone isomer in healthy opioid-naïve subjects and identify a safe and potentially effective dose range in this population These studies showed that REL-1017 was safe and well-tolerated at single oral doses up to 150 mg maximum tolerated dose and up to 75 mg administered once daily for 10 days in healthy opioid-naïve subjects
The pre-clinical and previous clinical experience with REL-1017 d-methadone provided the basis for the initiation of the present study which will extend the evaluation of the safety tolerability and PK of REL-1017 at 2 doses with repeated administration to depressed patients Since REL-1017 is proposed for use as adjunctive therapy in the treatment of patients diagnosed with major depressive disorder MDD the patients will be male adults with MDD who are diagnosed with a current depressive episode who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication
Based on the safety data from Protocol REL-1017-111 single doses of 5 mg 20 mg 60 mg 100 mg and 150 mg of REL-1017 or placebo were well tolerated The results of Protocol REL-1017-112 evaluated 10 days of dosing with 25 mg 50 mg and 75 mg of REL-1017 or placebo and no impact on safety was observed In spite of the confirmed dose proportionality the comparison of concentration and exposure between the 50 mg and 75 mg REL-1017 treatment groups demonstrated only slight differences Consequently 25 mg and 50 mg doses were chosen for administration in Protocol REL-1017-202 as single daily doses over a period of 7 days
Thus as a single isomer of racemic methadone d-methadone has been shown to possess NMDA antagonist properties with virtually no opioid activity or ketamine-like toxicities at the expected therapeutic doses
In this study adult male patients with MDD who are diagnosed with a current MDE and who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication will be randomized to study drug in a 111 ratio Approximately 15 patients each will receive REL-1017 25 mg REL-1017 50 mg or placebo once daily for 7 days Endpoints include assessments of safety tolerability efficacy and pharmacokinetics of REL-1017 Patients will be required to stay in the clinic for 10 days and will then be followed as an outpatient for 12 additional days
Racemic methadone the 5050 combination of d-methadone and l-methadone has been in widespread use for decades and has been studied extensively Methadone is currently approved for use in the management of severe pain detoxification treatment of opioid addiction and maintenance treatment of opioid addiction
The results of a study evaluating the receptor binding profiles of racemic methadone and its stereoisomers suggest that d-methadone does not essentially contribute to the opioid effect of racemic methadone and that it has a 10 times lower affinity for the mu1 mu2 and delta opioid receptors compared to l-methadone Racemic methadone and its d- and l isomers exhibit similar affinities for the non-competitive binding site of the NMDA receptor and are non-competitive NMDA receptor antagonists
In the forced swim test a rodent behavioral model of antidepressant activity both ketamine and d-methadone at all doses tested significantly decreased the immobility of the rats compared to the vehicle suggesting antidepressant like activity Neither drug increased spontaneous locomotor activity
Relmada has conducted 2 clinical studies to identify the dose levels of REL-1017 d-methadone that have little to no opioid effects and that are expected to possess NMDA antagonistic properties for the evaluation of oral REL-1017 in the treatment of MDD and neuropathic pain conditions Initial Phase 1 single ascending dose and multiple ascending dose clinical studies of REL-1017 were designed to evaluate the safety and tolerance of the pure d methadone isomer in healthy opioid-naïve subjects and identify a safe and potentially effective dose range in this population These studies showed that REL-1017 was safe and well-tolerated at single oral doses up to 150 mg maximum tolerated dose and up to 75 mg administered once daily for 10 days in healthy opioid-naïve subjects
The pre-clinical and previous clinical experience with REL-1017 d-methadone provided the basis for the initiation of the present study which will extend the evaluation of the safety tolerability and PK of REL-1017 at 2 doses with repeated administration to depressed patients Since REL-1017 is proposed for use as adjunctive therapy in the treatment of patients diagnosed with major depressive disorder MDD the patients will be male adults with MDD who are diagnosed with a current depressive episode who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication
Based on the safety data from Protocol REL-1017-111 single doses of 5 mg 20 mg 60 mg 100 mg and 150 mg of REL-1017 or placebo were well tolerated The results of Protocol REL-1017-112 evaluated 10 days of dosing with 25 mg 50 mg and 75 mg of REL-1017 or placebo and no impact on safety was observed In spite of the confirmed dose proportionality the comparison of concentration and exposure between the 50 mg and 75 mg REL-1017 treatment groups demonstrated only slight differences Consequently 25 mg and 50 mg doses were chosen for administration in Protocol REL-1017-202 as single daily doses over a period of 7 days
Thus as a single isomer of racemic methadone d-methadone has been shown to possess NMDA antagonist properties with virtually no opioid activity or ketamine-like toxicities at the expected therapeutic doses
In this study adult male patients with MDD who are diagnosed with a current MDE and who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication will be randomized to study drug in a 111 ratio Approximately 15 patients each will receive REL-1017 25 mg REL-1017 50 mg or placebo once daily for 7 days Endpoints include assessments of safety tolerability efficacy and pharmacokinetics of REL-1017 Patients will be required to stay in the clinic for 10 days and will then be followed as an outpatient for 12 additional days
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None