Putative Cognitive Enhancer VU319

NCT03220295 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: VU319
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a safety study of the molecule VU319 to ascertain pharmacokinetic and pharmacodynamic data and test cognitive enhancement in healthy volunteers.

Conditions

Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Frequency of adverse events per ascending dose cohort

  Change in adverse events frequency from Baseline to 144 hours post drug administration

Secondary Outcomes (14)

• Cognitive Battery - Critical Flicker Fusion (CFF)

  Baseline, 5 hours post drug administration

• Cognitive Battery - Choice Reaction Time (CRT)

  Baseline, 5 hours post drug administration

• Cognitive Battery - Spatial Selective Attention (Posner Task)

  Baseline, 5 hours post drug administration

• Cognitive Battery - Continuous Performance Test (Conners)

  Baseline, 5 hours post drug administration

• Cognitive Battery - Working Memory (N-Back Test)

  Baseline, 5 hours post drug administration

Study Arms (14)

Dose Escalation of VU319 - Dose 1

EXPERIMENTAL

Dose Escalation of VU319

Drug: Dose Escalation of VU319

Placebo - Dose 1

PLACEBO COMPARATOR

Dose Escalation of Placebo

Drug: Placebo Dose Escalation

Single Dose of VU319 under Fed State

EXPERIMENTAL

Single dose of VU319 (50% of the maximum tolerated dose) 30 minutes after a High Fat Standard Breakfast

Drug: Single Dose of VU319; Other: Fed State

Single Dose of Placebo under Fed State

PLACEBO COMPARATOR

Single dose of Placebo 30 minutes after a High Fat Standard Breakfast

Drug: Single Dose Placebo; Other: Fed State

Single Dose of VU319 under Fasted State

EXPERIMENTAL

Single dose of VU319 (50% of the maximum tolerated dose) after overnight fast

Drug: Single Dose of VU319; Other: Fasted State

Single Dose of Placebo under Fasted State

PLACEBO COMPARATOR

Single dose of placebo after overnight fast

Drug: Single Dose Placebo; Other: Fasted State

Dose Escalation of VU319 - Dose 2

EXPERIMENTAL

Dose Escalation of VU319

Drug: Dose Escalation of VU319

Dose Escalation of VU319 - Dose 3

EXPERIMENTAL

Dose Escalation of VU319

Drug: Dose Escalation of VU319

Dose Escalation of VU319 - Dose 4

EXPERIMENTAL

Dose Escalation of VU319

Drug: Dose Escalation of VU319

Dose Escalation of VU319 - Dose 5

EXPERIMENTAL

Dose Escalation of VU319

Drug: Dose Escalation of VU319

Placebo - Dose 2

PLACEBO COMPARATOR

Dose Escalation of Placebo

Drug: Placebo Dose Escalation

Placebo - Dose 3

PLACEBO COMPARATOR

Dose Escalation of Placebo

Drug: Placebo Dose Escalation

Placebo - Dose 4

PLACEBO COMPARATOR

Dose Escalation of Placebo

Drug: Placebo Dose Escalation

Placebo - Dose 5

PLACEBO COMPARATOR

Dose Escalation of Placebo

Drug: Placebo Dose Escalation

Interventions

Single Dose of VU319 DRUG

Single dose of VU319

Single Dose of VU319 under Fasted State; Single Dose of VU319 under Fed State

Single Dose Placebo DRUG

Single dose of placebo

Single Dose of Placebo under Fasted State; Single Dose of Placebo under Fed State

Fed State OTHER

drug is given 30 minutes after a high fat breakfast

Single Dose of Placebo under Fed State; Single Dose of VU319 under Fed State

Fasted State OTHER

drug is given after an overnight fast

Single Dose of Placebo under Fasted State; Single Dose of VU319 under Fasted State

Dose Escalation of VU319 DRUG

dose levels of the cohorts will be increased step wise

Dose Escalation of VU319 - Dose 1; Dose Escalation of VU319 - Dose 2; Dose Escalation of VU319 - Dose 3; Dose Escalation of VU319 - Dose 4; Dose Escalation of VU319 - Dose 5

Placebo Dose Escalation DRUG

dose levels of the cohorts will be increased step wise

Placebo - Dose 1; Placebo - Dose 2; Placebo - Dose 3; Placebo - Dose 4; Placebo - Dose 5

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged 18 through 55 years, inclusive.
• Body mass index 18 through 32 kg/m2
• Determined as healthy based on screening medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG (QTc interval with Fridericia's correction method recorded on screening and predose must be less than 450 msec for male and less than 470 in females).
• Clinical laboratory test result without clinically significant abnormalities at screening and at admission.
• Negative tests for Hepatitis B surface antigen, hepatitis C virus antibodies and human immunodeficiency virus (HIV-1 or HIV-2) antibody at screening.
• Nonsmokers (use of any nicotine containing product) or ex-smokers (have ceased smoking for at least 6 months and do not use any drug for smoking cessation).
• Negative screen for alcohol and drugs of abuse at screening and admission.
• For Women: Must have no child-bearing potential by reason of surgery or at least 1 year post-menopausal (i.e. 12 months without menstrual period), or menopause confirmed with an estradiol level of \< 30 pg/mL and follicle-stimulating hormone level of \> 40 IU/L at screening.
• For Men: Must be infertile (at least 3-months post-vasectomy), or truly abstinent of heterosexual intercourse, or heterosexual partner is not of child-bearing potential, or must agree to use an effective method of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository) through the study and for 28 days after last dose of study drug.
• Able and willing to be available for the duration of the study.
• Willing and able to give written informed consent to participate.
• Able to understand and comply with protocol instructions.
• Agrees not to receive any vaccination within 21 days prior to admission and through Day 7 after final discharge.
• Agrees not to use nonprescription drugs, including vitamins, antacids, and herbal and dietary supplements within 7 days prior to admission and through 7 days after final discharge. Acetaminophen may be used at doses of ≤ 1 g/day, and ibuprofen may be used at doses of ≤ 1.2 g/day starting no earlier than 48 hours after discharge.
• Agrees not to use nicotine-containing products from screening through 48 hours after discharge.

You may not qualify if:

• Individuals with significant previous or ongoing disease or disorder, on the basis of history, physical exam, ECG, and laboratory tests, including for example: Cardiovascular diseases; hypertension; cancer or neoplasia; diabetes; hepatic, endocrine, metabolic, respiratory, renal, gastrointestinal (except appendectomy), dermatological or hematological disorders, Axis I or II psychiatric, substance use, or cognitive disorders.
• Clinically significant infection or inflammation at time of screening or admission.
• Clinically significant abnormalities upon physical/neurological exam at screening.
• Acute gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea) at time of screening or admission
• History of seeking advice from a physician or counselor for abuse or misuse of alcohol, non-medical drugs, medicinal drugs or other substance abuse, for example, solvents.
• Any current or previous use of Class A drugs such as illicit opiate use, cocaine, ecstasy, LSD, and amphetamines (Class B). Volunteers that admit to occasional past use of cannabis will not be excluded as long as they have a negative drugs-of-abuse test at screening and admission and have been abstinent for at least 3 months.
• An alcoholic intake greater than 21 units per week or unwillingness to stop alcohol consumption for the duration of the study. Note: 1 unit = 8 g ethanol (250 mL of beer, 1 glass wine \[100 mL\], 1 measure spirits \[30 mL\]).
• Use of medication (including OTC and oral contraceptive agents) within 14 days of admission that may affect the safety of the subject or any study assessment, in the opinion of the investigator.
• Use of prescribed centrally active or psychoactive agents within 28 days from admission.
• Requirement for any medication that would need to be continued during the study.
• Use of any investigational medication within 3 months prior to the start of this study or scheduled to receive an investigational drug during the course of this study.
• Have participated in more than 2 clinical trials within the 12 months prior to screening
• History of blood donation in the last 3 months.
• History of severe allergies or multiple adverse drug reactions.
• Any condition, which compromises ability to give informed consent or to communicate with the investigator as required for the completion of this study.

Sponsors & Collaborators

• Vanderbilt University: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

Vanderbilt Medical Center

Nashville, Tennessee, 37212, United States

Location

Related Publications (1)

• Poslunsey MS, Wood MR, Han C, Stauffer SR, Panarese JD, Melancon BJ, Engers JL, Dickerson JW, Peng W, Noetzel MJ, Cho HP, Rodriguez AL, Hopkins CR, Morrison R, Crouch RD, Bridges TM, Blobaum AL, Boutaud O, Daniels JS, Kates MJ, Castelhano A, Rook JM, Niswender CM, Jones CK, Conn PJ, Lindsley CW. Discovery of VU0467319: an M1 Positive Allosteric Modulator Candidate That Advanced into Clinical Trials. ACS Chem Neurosci. 2025 Jan 1;16(1):95-107. doi: 10.1021/acschemneuro.4c00769. Epub 2024 Dec 11.

  PMID: 39660766 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Paul A Newhouse, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind safety study. The pharmacist is unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD/PI

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: July 18, 2017
• Study Start: July 28, 2017
• Primary Completion: October 30, 2019
• Study Completion: October 30, 2019
• Last Updated: February 6, 2020

Record last verified: 2020-02

Locations

US (1)