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

NCT04618263 | Terminated Phase 1 FDA Drug

• 1 other identifier: GATE-101-C-101
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Major Depressive Disorder; Excessive Sleepiness

Keywords

Major Depressive Disorder; Excessive Sleepiness; Metabotropic Glutamate Type 2/3 Receptor Antagonist

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment-Emergent Adverse Events Through Study Completion, 28 days

  Safety and Tolerabiity

  28 Days

Secondary Outcomes (4)

• Pharmacokinetics - maximum plasma concentration - following a single intravenous dose

  72 hours

• Pharmacokinetics - maximum plasma concentration - following 5 daily intravenous doses

  72 hours

• Pharmacokinetics - area under the curve - following a single intravenous dose

  72 hours

• Pharmacokinetics - area under the curve - following 5 daily intravenous doses

  72 hours

Study Arms (12)

GATE-101, 5 mg IV, Single Dose

EXPERIMENTAL

GATE-101, 5 mg IV, Single Dose, with follow up of 28 days

Drug: GATE-101

GATE-101, 15 mg IV, Single Dose

EXPERIMENTAL

GATE-101, 15 mg IV, Single Dose, with follow up of 28 days

Drug: GATE-101

GATE-101, 50 mg IV, Single Dose

EXPERIMENTAL

GATE-101, 50 mg IV, Single Dose, with follow up of 28 days

Drug: GATE-101

GATE-101, 150 mg IV, Single Dose

EXPERIMENTAL

GATE-101, 150 mg IV, Single Dose, with follow up of 28 days

Drug: GATE-101

GATE-101, 450 mg IV, Single Dose

EXPERIMENTAL

GATE-101, 450 mg IV, Single Dose, with follow up of 28 days

Drug: GATE-101

GATE-101, 15 mg IV, Single Dose, Lumbar Catheter

EXPERIMENTAL

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, 50 mg IV, Single Dose, Lumbar Catheter

EXPERIMENTAL

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 5 mg IV, Five Daily Doses

EXPERIMENTAL

GATE-101 5 mg IV, Five Daily Doses, with follow up for 28 days from first dose

Drug: GATE-101

GATE-101 15 mg IV, Five Daily Doses

EXPERIMENTAL

GATE-101 15 mg IV, Five Daily Doses, with follow up for 28 days from first dose

Drug: GATE-101

GATE-101 150 mg IV, Five Daily Doses

EXPERIMENTAL

GATE-101 150 mg IV, Five Daily Doses, with follow up for 28 days from first dose

Drug: GATE-101

Placebo Comparator, Single Dose

PLACEBO COMPARATOR

Placebo Comparator, Single Dose, with follow up for 28 days

Drug: GATE-101

Placebo Comparator, Five Daily Doses

PLACEBO COMPARATOR

Placebo Comparator, Five Daily Doses, with follow up for 28 days from first dose

Drug: GATE-101

Interventions

GATE-101 DRUG

GATE-101 is a metabotropic glutamate receptor type 2/3 antagonist

GATE-101 15 mg IV, Five Daily Doses; GATE-101 150 mg IV, Five Daily Doses; GATE-101 5 mg IV, Five Daily Doses; GATE-101, 15 mg IV, Single Dose; GATE-101, 15 mg IV, Single Dose, Lumbar Catheter; GATE-101, 150 mg IV, Single Dose; GATE-101, 450 mg IV, Single Dose; GATE-101, 5 mg IV, Single Dose; GATE-101, 50 mg IV, Single Dose; GATE-101, 50 mg IV, Single Dose, Lumbar Catheter; Placebo Comparator, Five Daily Doses; Placebo Comparator, Single Dose

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normal, healthy volunteer male and female subjects
• Aged 18 to 40 years
• 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.
• 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.
• Body mass index (BMI) \< 30
• Clinical laboratory values \<2 times the upper limit of normal (ULN) or deemed not clinically significant by the Investigator.
• 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.

You may not qualify if:

• Human immunodeficiency virus (HIV) infection, or hepatitis or other ongoing infectious disease
• 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
• Current abuse of illicit substances, using the Diagnostic and Statistical Manual (DSM) V definition of substance use disorder.
• 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.
• Currently pregnant, planning to become pregnant during the course of the study, or nursing mother
• Impaired renal function (GFR \< 90 ml/min)
• 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
• Type I or Type II diabetes
• 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
• 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.
• History of allergy or sensitivity, or intolerance to NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone
• Received another investigational drug or device within 30 days of enrollment in this study
• Previously participated in this study
• 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
• 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.

Sponsors & Collaborators

• Syndeio Biosciences, Inc: lead

Study Sites (1)

Clinilabs Drug Development Corporation

Eatontown, New Jersey, 07724, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Disorders of Excessive Somnolence

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Ronald M Burch, MD, PhD

  Syndeio Biosciences, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Triple, Participant, Investigator, Outcomes Assessor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: October 31, 2020
• First Posted: November 5, 2020
• Study Start: October 26, 2020
• Primary Completion: August 13, 2021
• Study Completion: August 13, 2021
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

US (1)