The Tolerability and Effects of AZD0530 in Individuals With or Without a Family History of Alcoholism

NCT02262026 | Completed Phase 1 DMC

• 1 other identifier: 1503015528
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Functional neuroimaging of alcoholism vulnerability: glutamate, reward, impulsivity, and Pavlovian-to-instrumental transfer (PIT), part II Saracatinib

Conditions

Alcoholism

Outcome Measures

Primary Outcomes (1)

• BOLD activation during A1 phase

  BOLD activation during the A1 phase of the MRI Monetary Incentive Delay task

  4 Hours post medication administration

Secondary Outcomes (1)

• BOLD signal activation in the anterior cingulate cortex(ACC)

  4 Hours post medication administration

Study Arms (12)

FHP; 125mg AZD0530, then 50mg AZD0530, then placebo

EXPERIMENTAL

Family History positive for alcoholism will take place in blinded testing of 125 mg, then 50 mg, then placebo separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHP; 125mg AZD0530, then placebo, then 50mg AZD0530

EXPERIMENTAL

Family History positive for alcoholism will take place in blinded testing of 125 mg, then placebo, then 50mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHP; 50mg AZD0530, then 125mg AZD0530, then placebo

EXPERIMENTAL

Family History positive for alcoholism will take place in blinded testing of 50mg, then 125mg, then placebo separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHP; 50mg AZD0530, then placebo, then 125mg AZD0530

EXPERIMENTAL

Family History positive for alcoholism will take place in blinded testing of 50mg, then placebo, then 125mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHP; placebo, then 50mg AZD0530, then 125mg AZD0530

EXPERIMENTAL

Family History positive for alcoholism will take place in blinded testing of placebo, then 50 mg, then 125 mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHP; placebo, then 125mg AZD0530,then 50mg AZD0530

EXPERIMENTAL

Family History positive for alcoholism will take place in blinded testing of placebo, then 125 mg, then 50 mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHN; 125mg AZD0530, then 50mg AZD0530, then placebo

ACTIVE COMPARATOR

Family History negative for alcoholism will take place in blinded testing of 125 mg, then 50 mg, then placebo separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHN; 125mg AZD0530, then placebo, then 50mg AZD0530

ACTIVE COMPARATOR

Family History negative for alcoholism will take place in blinded testing of 125 mg, then placebo, then 50mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHN; 50mg AZD0530, then 125mg AZD0530, then placebo

ACTIVE COMPARATOR

Family History negative for alcoholism will take place in blinded testing of 50mg, then 125mg, then placebo separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHN; 50mg AZD0530, then placebo, then 125mg AZD0530

ACTIVE COMPARATOR

Family History negative for alcoholism will take place in blinded testing of 50mg, then placebo, then 125mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHN; placebo, then 50mg AZD0530, then 125mg AZD0530

ACTIVE COMPARATOR

Family History negative for alcoholism will take place in blinded testing of placebo, then 50 mg, then 125 mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

FHN; placebo, then 125mg AZD0530, then 50mg AZD0530

ACTIVE COMPARATOR

Family History negative for alcoholism will take place in blinded testing of placebo, then 125 mg, then 50 mg separated by 1 week for each test

Drug: 125 mg AZD0530; Drug: 50 mg AZD0530; Drug: Placebo

Interventions

125 mg AZD0530 DRUG

Randomized to receive 125 mg of AZD0530

Also known as: saracatinib, AZD0530

FHN; 125mg AZD0530, then 50mg AZD0530, then placebo; FHN; 125mg AZD0530, then placebo, then 50mg AZD0530; FHN; 50mg AZD0530, then 125mg AZD0530, then placebo; FHN; 50mg AZD0530, then placebo, then 125mg AZD0530; FHN; placebo, then 125mg AZD0530, then 50mg AZD0530; FHN; placebo, then 50mg AZD0530, then 125mg AZD0530; FHP; 125mg AZD0530, then 50mg AZD0530, then placebo; FHP; 125mg AZD0530, then placebo, then 50mg AZD0530; FHP; 50mg AZD0530, then 125mg AZD0530, then placebo; FHP; 50mg AZD0530, then placebo, then 125mg AZD0530; FHP; placebo, then 125mg AZD0530,then 50mg AZD0530; FHP; placebo, then 50mg AZD0530, then 125mg AZD0530

50 mg AZD0530 DRUG

Randomized to receive 50 mg of AZD0530

Also known as: saracatinib, AZD0530

FHN; 125mg AZD0530, then 50mg AZD0530, then placebo; FHN; 125mg AZD0530, then placebo, then 50mg AZD0530; FHN; 50mg AZD0530, then 125mg AZD0530, then placebo; FHN; 50mg AZD0530, then placebo, then 125mg AZD0530; FHN; placebo, then 125mg AZD0530, then 50mg AZD0530; FHN; placebo, then 50mg AZD0530, then 125mg AZD0530; FHP; 125mg AZD0530, then 50mg AZD0530, then placebo; FHP; 125mg AZD0530, then placebo, then 50mg AZD0530; FHP; 50mg AZD0530, then 125mg AZD0530, then placebo; FHP; 50mg AZD0530, then placebo, then 125mg AZD0530; FHP; placebo, then 125mg AZD0530,then 50mg AZD0530; FHP; placebo, then 50mg AZD0530, then 125mg AZD0530

Placebo DRUG

Placebo

FHN; 125mg AZD0530, then 50mg AZD0530, then placebo; FHN; 125mg AZD0530, then placebo, then 50mg AZD0530; FHN; 50mg AZD0530, then 125mg AZD0530, then placebo; FHN; 50mg AZD0530, then placebo, then 125mg AZD0530; FHN; placebo, then 125mg AZD0530, then 50mg AZD0530; FHN; placebo, then 50mg AZD0530, then 125mg AZD0530; FHP; 125mg AZD0530, then 50mg AZD0530, then placebo; FHP; 125mg AZD0530, then placebo, then 50mg AZD0530; FHP; 50mg AZD0530, then 125mg AZD0530, then placebo; FHP; 50mg AZD0530, then placebo, then 125mg AZD0530; FHP; placebo, then 125mg AZD0530,then 50mg AZD0530; FHP; placebo, then 50mg AZD0530, then 125mg AZD0530

Eligibility Criteria

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

You may qualify if:

• Clear History of a father having a history of alcoholism, OR a mother AND another 1st or 2nd degree relative having a history of alcoholism, OR no 1st or 2nd degree relatives with alcoholism or substance abuse

You may not qualify if:

• Current diagnosis of DSM-IV-TR Axis I disorder, or past diagnosis of any substance use disorder or moderate alcohol use disorder
• Report of psychotic disorder in a 1º relative
• Auditory or visual impairment that interferes with test taking
• History of prenatal exposure to alcohol plus currently meeting criteria for features of fetal alcohol syndrome
• Not speaking English fluently or being a non-native English speaker, or being educated in a primary language other than English \>grade 1
• Mental retardation (Full Scale IQ\<70) using 2 WASI subtests for IQ estimate
• Traumatic brain injury with loss of consciousness \> 30 minutes, or concussion in last 30 days
• Presence or history of any medical/neurologic illness that may affect brain physiology (e.g., epilepsy, Multiple Sclerosis), including focal brain lesion seen on structural MRI (all structural scans are read by a licensed radiologist)
• Current pregnancy (all females will be tested with urine screens on the day of MRI and prior to each phase of drug treatment)
• Positive urine screen for the presence of marijuana, cocaine, opiates or breath screen to detect the presence of alcohol, administered at each lab visit.
• Inability to comprehend the consent form appropriately
• Ferromagnetic metal devices, clips or fragments in body (orbital x-ray performed if needed).
• Current use (within 30 days of screening) of specific psychoactive medications (e.g., typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity, etc.). Current use of warfarin.
• Current use of the following medications (CYP3A4 substrates whose metabolism may be slowed by AZD0530): carbamazepine, colchicine, cyclosporine, disopyramide, fluticasone, quinidine, vinblastine, vincristine, nifedipine. Patients taking sildenafil, tadalafil, and vardenafil will be advised to stop taking these medications for the duration of the trial. Patients cannot take the following drugs which inhibit the CYP3A4 isoenzyme: cimetidine, cyclosporine, danazol, fluconazole, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole, macrolides, miconazole, nefazodone, omeprazole, ritonavir, and verapamil, aromatase inhibitors, docetaxel
• Neutropenia defined as absolute neutrophils count of \<1,500/microliter.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

saracatinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Godfrey D Pearlson, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: October 10, 2014
• Study Start: November 1, 2014
• Primary Completion: April 26, 2019
• Study Completion: April 26, 2019
• Last Updated: February 24, 2023

Record last verified: 2023-02

Locations

US (1)