NMDA Receptor Modulation for Hyperarousal in PTSD

NCT03166501 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 363711R61MH110540-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1b study examines the safety and efficacy of parenterally-administered lanicemine in a parallel-arm, randomized, double-blind, placebo-controlled trial in adult patients (N=24) with significant PTSD symptoms and elevated anxiety potentiated startle (APS). Investigator hypothesize that lanicemine (100 mg) displays a normalization of APS following three infusions over 5 non-consecutive days. If target engagement is demonstrated and the drug is safe and tolerable in this patient population, investigator will proceed to a larger POC study.

Conditions

Depression; Post Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Primary Objective

  Primary Objective is to examine, relative to placebo, whether lanicemine will demonstrate normalization of the APS response following three treatments.

  24 months

Secondary Outcomes (4)

• Secondary Objectives (1/4)

  24 months

• Secondary Objectives (2/4)

  24 months

• Secondary Objectives (3/3)

  24 months

• Secondary Objectives (4/4)

  24 months

Study Arms (2)

Treatment

EXPERIMENTAL

Lanicemine 100mg Intravenous

Drug: Lanicemine

Placebo

PLACEBO COMPARATOR

Normal saline Intravenous

Drug: Placebo

Interventions

Lanicemine DRUG

Three 60 min parenteral infusions over a 5 day period

Also known as: BHV-5500

Treatment

Placebo DRUG

Three 60 min parenteral infusions over a 5 day period

Also known as: Baxter

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Patients must provide acceptable proof of identity documentation to confirm initials and date of birth
• Male and female patients aged 21 to 65 years, inclusive.
• All male patients who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of IP until 12 weeks after their last dose. All females must have a negative serum pregnancy test. Women of childbearing potential (WOCBP, see below) must use a highly effective form of birth control plus the use of a condom by the male sexual partner, reviewed and approved by the PI. The highly effective form of birth control includes: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective IUD/IUS, Depo-Provera injections, oral contraceptive, and Evra Patch or Nuvaring. Women should be on a stable method of birth control for a minimum of 3 months , prior to randomization and 3 months after the last dose of IP.
• Women of non-childbearing potential. Women of non-childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they are amenorrheic for 12 months prior to randomization without an alternative medical cause. The following age-specific requirements apply:
• Women \< 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Women ≥ 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
• CAPS-5 score ≥ 25 and CGI-S ≥ 4 at Screening and Randomization
• Anxiety Potentiated Startle T-score ≥ 2.8.
• Psychotropic medications must remain at a stable dose for at least 42 days prior to screening, without clinically significant adjustment.
• Be able to understand and comply with the requirements of the study, as judged by the investigator

You may not qualify if:

• Patients who are currently participating in another clinical study in which the patient is exposed to an investigational or non-investigational drug or device, or have done so within the last 30 days prior to screening.
• Patients who have no regular contact with an adult who could come to the patient's aid should an urgent need arise.
• Currently being treated with MAOIs, lithium, divalproex, carbamazepine, barbiturates, or benzodiazepines. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor \[eg, riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine\], or the mu-opioid receptor.
• Patients who meet DSM-5 criteria for substance use disorder (amphetamines, cocaine, hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics) within 1 month prior to screening. Patients with a positive urine drug screen (UDS) are excluded except for patients testing positive for prescribed medications that are otherwise permitted and there is no evidence of misuse or abuse. Patients can be re-tested only if either the initial opiate or barbiturate result is positive and they have a prescription, but the patient should be excluded if the result is still positive at the second test. Patients with positive UDS for drug(s) legally available by prescription must provide evidence of prescription for the drug(s).
• Patients with a binge-pattern of alcohol use which makes them at risk for withdrawal-related seizures. Also, significant alcohol withdrawal symptoms that require medical detoxification.
• Patients with a suicide attempt within the last 3 months or at imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigator.
• Patients who are pregnant or lactating.
• Clinically significant laboratory value, physical examination, or ECG that signifies a major medical illness that is unstable or inadequately controlled, or that may put the subject at risk during the study in the judgment of the investigator. Hypothyroidism is permitted if corrected and the patient is on a stable treatment regimen for a minimum of 6 months.
• Patients with any history of seizure disorder (except for febrile seizures in childhood) or traumatic brain injury.
• Previous exposure to lanicemine.
• Patients with a personality disorder which in the opinion of the investigator has a major impact on the patient's current psychiatric status and would preclude safe study participation.
• Body mass index (BMI) ≥ 40 kg/m2

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Michael E. DeBakey VA Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (5)

• Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database Syst Rev. 2024 May 20;5(5):CD013613. doi: 10.1002/14651858.CD013613.pub2.

  PMID: 38767196 DERIVED

• Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Feb 10;2(2):CD013443. doi: 10.1002/14651858.CD013443.pub2.

  PMID: 35141873 DERIVED

• Ramakrishnan N, Lijffijt M, Green CE, Balderston NL, Murphy N, Grillon C, Iqbal T, Vo-Le B, O'Brien B, Murrough JW, Swann AC, Mathew SJ. Neurophysiological and clinical effects of the NMDA receptor antagonist lanicemine (BHV-5500) in PTSD: A randomized, double-blind, placebo-controlled trial. Depress Anxiety. 2021 Nov;38(11):1108-1119. doi: 10.1002/da.23194. Epub 2021 Jul 12.

  PMID: 34254405 DERIVED

• Murphy N, Lijffijt M, Ramakrishnan N, Vo-Le B, Vo-Le B, Iqbal S, Iqbal T, O'Brien B, Smith MA, Swann AC, Mathew SJ. Does mismatch negativity have utility for NMDA receptor drug development in depression? Braz J Psychiatry. 2022 Jan-Feb;44(1):61-73. doi: 10.1590/1516-4446-2020-1685.

  PMID: 33825765 DERIVED

• Lijffijt M, Green CE, Balderston N, Iqbal T, Atkinson M, Vo-Le B, Vo-Le B, O'Brien B, Grillon C, Swann AC, Mathew SJ. A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD. Front Psychiatry. 2019 Dec 13;10:846. doi: 10.3389/fpsyt.2019.00846. eCollection 2019.

  PMID: 31920733 DERIVED

MeSH Terms

Conditions

Depression; Stress Disorders, Post-Traumatic

Interventions

AZD6765

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 25, 2017
• Study Start: September 1, 2018
• Primary Completion: November 12, 2019
• Study Completion: November 14, 2019
• Last Updated: August 19, 2020

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)