Safety and Tolerability of Single and Multiple Ascending Doses of GATE-101 in Normal Human Volunteers

A Randomized Double-blind, Placebo-controlled Single and Multiple Intravenous Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of GATE-101 in Normal Healthy Volunteers

To evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of GATE-101 in normal human volunteers

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder; Excessive Sleepiness
• Intervention / Treatment: Drug: GATE-101

Detailed Description

Single ascending dose (SAD), multiple ascending dose (MAD), double-blind placebo-controlled study in normal human volunteers.

Secondary objectives:

To evaluate the pharmacokinetics (PK) of GATE-101 following increasing single and multiple doses of intravenously (IV) administered GATE-101.

GATE-101 or Placebo: Dose/Mode of Administration: Single or 5 Daily Doses;Intravenous

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Clinilabs Drug Development Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Normal, healthy volunteer male and female subjects
2. Aged 18 to 40 years

3. For female subjects must meet one of the following:

   • Surgically sterile or at least 2 years menopausal, confirmed by follicle stimulating hormone (FSH) at screening visit, or,
   • If of childbearing potential, subject must use an acceptable method of birth control from date of screening to at least 30 days after the last dose of study drug. Must have a documented negative blood or urine pregnancy test within 24 hours prior to dosing. If reported sterile or postmenopausal, will be confirmed by FSH.

4. For male subjects, must meet one of the following:

   • Surgically sterile
   • If not surgically sterile then use of an acceptable form of contraception (condom) from the time of randomization through 30 days following the last dose of study drug. Male subjects are strongly advised to inform female partners of the need for them to use highly effective birth control during this time period.
5. Body mass index (BMI) < 30
6. Clinical laboratory values <2 times the upper limit of normal (ULN) or deemed not clinically significant by the Investigator.
7. Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments.

Exclusion Criteria:

1. Human immunodeficiency virus (HIV) infection, or hepatitis or other ongoing infectious disease
2. Evidence of alcohol abuse (greater than 4 units of alcohol on most days; 1 unit = 1/2 pint of beer, 1 glass of wine or 1 oz. of spirits). Alcohol consumption should be avoided for at least 24 hours prior to baseline/dosing visit. A positive alcohol breathalyzer at screening and baseline visit
3. Current abuse of illicit substances, using the Diagnostic and Statistical Manual (DSM) V definition of substance use disorder.
4. Current cigarette/tobacco smoker or use of other tobacco or nicotine products including ecigarettes or vaping (if formerly a smoker must not have smoked for at least one year prior to enrolling in this study). Nonsmoking will be confirmed by cotinine assay.
5. Currently pregnant, planning to become pregnant during the course of the study, or nursing mother
6. Impaired renal function (GFR < 90 ml/min)
7. Elevated systolic blood pressure (> 130 mmHg) or diastolic blood pressure (> 80 mmHg) and/or increased QTc (>450 msec for men or >470 msec for women) or additional risk factors for Torsades de Pointes including heart failure, hypokalemia, family history of Long QT Syndrome
8. Type I or Type II diabetes
9. Malignancy in the last 5 years, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix
10. Currently taking prescription (except as listed in Section 7.4.1) or over-the-counter medications including herbal therapies, within 14 days of enrollment into the study.
11. History of allergy or sensitivity, or intolerance to NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone
12. Received another investigational drug or device within 30 days of enrollment in this study
13. Previously participated in this study
14. Psychiatric disease including major depression, bipolar disorder, anxiety, or schizophrenia, or other medical condition that, in the opinion of the Investigator, would interfere with the evaluation of study drug safety
15. For subjects in lumbar catheter Groups (6 and 7) has a history of excessive bleeding after invasive procedures or surgery or known coagulation or platelet abnormality, or has been on any blood thinner or medication affecting platelet function, such as aspirin, nonsteroidal anti-inflammatory medications, corticosteroids (except topical) or warfarin within the 7 days prior to enrollment, or has known allergy to any anesthetic agent that may be used for the lumbar puncture.
16. For subjects in lumbar catheter Groups (6 and 7) has a history of infection that required IV antibiotics within the 45 days or oral antibiotics within 30 days prior to enrollment, and, at the time of clinic admission, be febrile or have signs/symptoms consistent with an infection.
17. For subjects in lumbar catheter Groups (6 and 7) has a history of or physical examination evidence of a lumbar spine abnormality that may preclude placement of a spinal catheter, presence of intraspinal shunt devices (e.g. ventriculoperitoneal shunt), or history of elevated intracranial pressure, normal pressure hydrocephalus, or other neurological condition that in the opinion of the Investigator precludes safe study participation.
18. In the opinion of the Investigator, the Safety Monitor, or the Sponsor Study Monitor, has a history of severe renal or hepatic impairment, severe active hepatic disease, or other clinically significant medical condition that may preclude safe study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GATE-101, 5 mg IV, Single Dose; GATE-101, 5 mg IV, Single Dose, with follow up of 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101, 15 mg IV, Single Dose; GATE-101, 15 mg IV, Single Dose, with follow up of 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101, 50 mg IV, Single Dose; GATE-101, 50 mg IV, Single Dose, with follow up of 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101, 150 mg IV, Single Dose; GATE-101, 150 mg IV, Single Dose, with follow up of 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101, 450 mg IV, Single Dose; GATE-101, 450 mg IV, Single Dose, with follow up of 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101, 15 mg IV, Single Dose, Lumbar Catheter; GATE-101, 15 mg IV, Single Dose, with Lumbar Catheter for collection of cerebrospinal fluid (CSF) PK samples, with follow up of 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101, 50 mg IV, Single Dose, Lumbar Catheter; GATE-101, 50 mg IV, Single Dose, with Lumbar Catheter for collection of cerebrospinal fluid (CSF) PK samples, with follow up of 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101 5 mg IV, Five Daily Doses; GATE-101 5 mg IV, Five Daily Doses, with follow up for 28 days from first dose	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101 15 mg IV, Five Daily Doses; GATE-101 15 mg IV, Five Daily Doses, with follow up for 28 days from first dose	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Experimental: GATE-101 150 mg IV, Five Daily Doses; GATE-101 150 mg IV, Five Daily Doses, with follow up for 28 days from first dose	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Placebo Comparator: Placebo Comparator, Single Dose; Placebo Comparator, Single Dose, with follow up for 28 days	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist
Placebo Comparator: Placebo Comparator, Five Daily Doses; Placebo Comparator, Five Daily Doses, with follow up for 28 days from first dose	Drug: GATE-101; GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-Emergent Adverse Events Through Study Completion, 28 days	Safety and Tolerabiity	28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - maximum plasma concentration - following a single intravenous dose	Maximum observed plasma concentration following a single dose	72 hours
Pharmacokinetics - maximum plasma concentration - following 5 daily intravenous doses	Maximum observed plasma concentration following the fifth daily doses	72 hours
Pharmacokinetics - area under the curve - following a single intravenous dose	Area under the concentration time curve from time 0 to infinity following a single dose	72 hours
Pharmacokinetics - area under the curve - following 5 daily intravenous doses	Area under the concentration time curve from time 0 to infinity following the fifth daily dose	72 hours

Collaborators and Investigators

• Sponsor: Gate Neurosciences, Inc
• Investigators: Study Director: Ronald M Burch, MD, PhD, Gate Neurosciences, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2020
• Primary Completion (Actual): August 13, 2021
• Study Completion (Actual): August 13, 2021

Study Registration Dates

• First Submitted: October 31, 2020
• First Submitted That Met QC Criteria: October 31, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; Excessive Sleepiness; Metabotropic Glutamate Type 2/3 Receptor Antagonist
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Sleepiness
• Other Study ID Numbers: GATE-101-C-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No