A Novel Compound for Alcoholism Treatment: A Translational Strategy - Part II

NCT02707055 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16008016-DA-0080
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Hormones are naturally occurring chemicals in the body. Ghrelin is a hormone that stimulates appetite. It may also stimulate alcohol cravings and use. Researchers want to learn more about alcohol cravings and test if a drug that blocks ghrelin lowers alcohol cravings. Objective: To test if the drug PF-05190457 decreases alcohol craving. Eligibility: People ages 18-70 who have: Alcohol use disorder No other serious medical problems Woman must be postmenopausal or have had surgery to prevent pregnancy. Design: Participants will stay on the inpatient unit here at the Clinical Center for two 2-week stages, which will be separated by at least 2 days. The inpatient phase include: Taking the study drug or placebo by mouth twice daily Blood tests Tasting several sweet solutions Physical exams Exposure to alcohol, water, and food cues in a bar-like room. Participants answer questions on a computer. Blood pressure and heart rate are monitored through an arm cuff and sensors on the chest. MRIs: Participants lie on a table that slides in and out of the cylinder, and a coil is placed over the head. They complete tasks on a computer screen while in the cylinder. This lasts up to 2 hours. Wearing a virtual reality headset, walking around a virtual room, and selecting virtual food and drink. Physical exams

Conditions

Alcoholism

Keywords

Alcohol Consumption; Alcohol Treatment; Alcoholism; Ghrelin; Ghrelin Antagonism

Outcome Measures

Primary Outcomes (1)

• Alcohol Cue-elicited Craving Assessed in a "Bar-like" Laboratory

  Alcohol cue elicited craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  96 minutes

Secondary Outcomes (1)

• Food Choices in a "Virtual Buffet" Conducted in a Virtual Reality Context.

  40 minutes

Study Arms (2)

PF-05190457, then placebo

EXPERIMENTAL

Participants with alcohol use disorder received PF-05190457 100 mg twice a day for a maximum of 14 days followed by a minimum of 2-day washout period, then placebo twice a day for a maximum of 14 days.

Drug: PF-05190457; Other: Placebo

Placebo, then PF-05190457

PLACEBO COMPARATOR

Participants with alcohol use disorder received placebo twice a day for a maximum of 14 days followed by a minimum of 2-day washout period then PF-05190457 100 mg twice a day for a maximum of 14 days.

Drug: PF-05190457; Other: Placebo

Interventions

PF-05190457 DRUG

Ghrelin Receptor Inverse Agonist

PF-05190457, then placebo; Placebo, then PF-05190457

Placebo OTHER

Placebo

PF-05190457, then placebo; Placebo, then PF-05190457

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female individuals 18-70 years old (inclusive)
• Current Alcohol Use Disorder (AUD) by DSM-5 criteria based on the SCID
• Most recent urine drug test for illegal drugs of abuse is negative
• Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score is less than or equal to 8
• Heart rate less than or equal to 100 on two separate measurements, both assessed after CIWA-Ar score is less than or equal to 8
• Female subjects must be of non childbearing potential as defined by at least one of the following criteria:
• a) Females 45-70 years old, who are menopausal, defined as follow:
• i) Females who are between 45-55 years old: they will be considered menopausal if they satisfy all the following three requirements during screening: 1) they are in amenorrhea, defined as absence of menstruation for the previous 12 months; 2) they have a negative urine pregnancy test; and 3) they have a serum FSH level within the laboratory s reference range for postmenopausal females.
• ii) Females who are between 56-70 years old: they will be considered menopausal if they are in amenorrhea, defined as absence of menstruation for the previous 12 months before screening.
• b) Females 21-70 years old, who have a documented hysterectomy and/or bilateral oophorectomy.
• All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy) will be considered to be of childbearing potential.
• Male subjects must use one of the following methods of contraception from the first dose of study medication and until 28 days after dosing (given that it is unknown whether the effects of this drug can cause birth defects):
• Abstinence.
• A condom AND one of the following:
• Vasectomy for more than 6 months.

You may not qualify if:

• Lifetime clinical diagnosis of schizophrenia or bipolar disorder
• EKG with QTc \> 450 msec as determined by the Fridericia formulas.
• BMI less than or equal to 18.5 kg/M(2) or anorexia
• BMI greater than or equal to 40 kg/m(2)
• History of epilepsy and/or seizures
• NOTE: individuals who have a history of alcohol withdrawal seizures may be in the study as long as they have been abstinent from alcohol for at least 2 weeks prior to consent and during that period of abstinence, there were no seizure episodes (otherwise, participant remains not eligible).
• Most recent blood tests show creatinine greater than or equal to 2 mg/dL, AST or ALT \> 3 times the upper normal limit, hemoglobin \<10.5 g/dl
• Subjects who have diabetes and/or are treated with any drug with glucose lowering properties such as sulfonylurea, insulin, metformin, thiazolidinediones (TZD), Dipeptidyl peptidase-4 (DPP4) inhibitors, or Glucagon-like peptide-1(GLP-1)agonists (due to the glucose-lowering properties of PF-05190457 observed in healthy volunteers)
• A. Naltrexone, acamprosate, alcohol dehydrogenase inhibitors, topiramate, gabapentin, ondansetron, benzodiazepines, baclofen, drugs that are known to prolong the QTc interval and barbiturates as well as hormone replacement therapy; medications and dietary/herbal supplements (like St. John's wort) that interact with Cytochrome P450 3A4. Patients who take these medications may be enrolled in the study only if the potentially interacting medication has been stopped for a period of at least 5 half-lives of the interacting medication before PF-05190457 administration. Patients who take these medications on an as needed (PRN) schedule or take
• the medication as a one-time dose as part of a medical procedure or a diagnostic test, for example, may not have to wait the 5 half-lives period of time before enrollment; this will be evaluated on a case by case basis by the MAI and/or PI, based on the specific pharmacological properties of the medication.
• Unable to pass a finger rub hearing test
• Vision is unable to be corrected to (Snellen) 20/100
• Clinically-significant history of motion or car sickness, or history of vestibular disorders
• Any other reason or clinical condition for which the PI or the MAI will consider unsafe for a possible participant to participate in this study
• Have contraindications for brain fMRI, as determined by the NIAAA MRI Safety screening form (conducted under the 14-AA-0181 Screening Protocol)

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead
• National Institute on Drug Abuse (NIDA): collaborator
• University of Rhode Island: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Tyler RE, Pfaff RK, Khan RMN, Loften A, Zurick R, Zeng Y, Arisa OT, Harvey C, Akhlaghi F, Figg WD, Farokhnia M, Leggio L. Pharmacokinetic and pharmacodynamic results from a randomized controlled study with the growth hormone secretagogue receptor blocker PF-5190457 in recently abstinent patients with alcohol use disorder. Int J Neuropsychopharmacol. 2026 Feb 2;29(2):pyaf081. doi: 10.1093/ijnp/pyaf081.

  PMID: 41474196 DERIVED

• Faulkner ML, Farokhnia M, Lee MR, Farinelli L, Browning BD, Abshire K, Daurio AM, Munjal V, Deschaine SL, Boukabara SR, Fortney C, Sherman G, Schwandt M, Akhlaghi F, Momenan R, Ross TJ, Persky S, Leggio L. A randomized, double-blind, placebo-controlled study of a GHSR blocker in people with alcohol use disorder. JCI Insight. 2024 Dec 20;9(24):e182331. doi: 10.1172/jci.insight.182331.

  PMID: 39704175 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking

Interventions

PF-5190457

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Behavior

Limitations and Caveats

Early termination of the study due to the COVID-19 pandemic resulted in a smaller number of participants analyzed, compared to the planned sample.

Results Point of Contact

• Title: Dr. Lorenzo Leggio, M.D., PhD
• Organization: National Institute on Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA)

lorenzo.leggio@nih.gov

+1 443 740 2801

Study Officials

• Lorenzo Leggio, M.D., PhD

  National Institute on Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: March 14, 2016
• Study Start: June 15, 2016
• Primary Completion: February 20, 2020
• Study Completion: September 9, 2020
• Last Updated: March 16, 2022
• Results First Posted: March 16, 2022

Record last verified: 2021-10

Locations

US (1)