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

A Phase One Study Investigating the Tolerability and Effects of AZD0530 on Functional Neuroimaging Responses in Individuals With or Without a Family History of Alcoholism

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

Study Overview

• Status: Completed
• Conditions: Alcoholism
• Intervention / Treatment: Drug: Placebo; Drug: 125 mg AZD0530; Drug: 50 mg AZD0530

Detailed Description

To assess the effect of oral AZ D0530 at various doses on neuroimaging parameters associated with various forms of impulsivity mediated through glutamate-dopamine interactions, as ascertained through functional magnetic resonance imaging. -- --NOTE-- AZD0530 dosage of 50mg was discontinued by manufacturer. Adjustments were made to account for the removal of the 50mg dosage in all arms of the study.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

1. Current diagnosis of DSM-IV-TR Axis I disorder, or past diagnosis of any substance use disorder or moderate alcohol use disorder
2. Report of psychotic disorder in a 1º relative
3. Auditory or visual impairment that interferes with test taking
4. History of prenatal exposure to alcohol plus currently meeting criteria for features of fetal alcohol syndrome
5. Not speaking English fluently or being a non-native English speaker, or being educated in a primary language other than English >grade 1
6. Mental retardation (Full Scale IQ<70) using 2 WASI subtests for IQ estimate
7. Traumatic brain injury with loss of consciousness > 30 minutes, or concussion in last 30 days
8. 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)
9. Current pregnancy (all females will be tested with urine screens on the day of MRI and prior to each phase of drug treatment)
10. Positive urine screen for the presence of marijuana, cocaine, opiates or breath screen to detect the presence of alcohol, administered at each lab visit.
11. Inability to comprehend the consent form appropriately
12. Ferromagnetic metal devices, clips or fragments in body (orbital x-ray performed if needed).
13. 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.
14. 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
15. Neutropenia defined as absolute neutrophils count of <1,500/microliter.
16. Thrombocytopenia defined as platelet count <100x103/microliter.
17. AST, ALT, total bilirubin >1.5 times upper normal; serum creatinine, >2 time upper normal limit, total bilirubin>1.5 times ULN; Serum creatinine >2.0 times ULN.
18. History of interstitial lung disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FHP; 125mg AZD0530, then 50mg AZD0530, then placebo; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Experimental: FHP; 125mg AZD0530, then placebo, then 50mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Experimental: FHP; 50mg AZD0530, then 125mg AZD0530, then placebo; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Experimental: FHP; 50mg AZD0530, then placebo, then 125mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Experimental: FHP; placebo, then 50mg AZD0530, then 125mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Experimental: FHP; placebo, then 125mg AZD0530,then 50mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Active Comparator: FHN; 125mg AZD0530, then 50mg AZD0530, then placebo; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Active Comparator: FHN; 125mg AZD0530, then placebo, then 50mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Active Comparator: FHN; 50mg AZD0530, then 125mg AZD0530, then placebo; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Active Comparator: FHN; 50mg AZD0530, then placebo, then 125mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Active Comparator: FHN; placebo, then 50mg AZD0530, then 125mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib
Active Comparator: FHN; placebo, then 125mg AZD0530, then 50mg AZD0530; 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: Placebo; Placebo; Drug: 125 mg AZD0530; Randomized to receive 125 mg of AZD0530; Other Names: AZD0530; saracatinib; Drug: 50 mg AZD0530; Randomized to receive 50 mg of AZD0530; Other Names: AZD0530; saracatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD activation during A1 phase	BOLD activation during the A1 phase of the MRI Monetary Incentive Delay task	4 Hours post medication administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD signal activation in the anterior cingulate cortex(ACC)	BOLD signal activation in the anterior cingulate cortex (ACC) observed during False Alarms of the GoNoGo Task	4 Hours post medication administration

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): April 26, 2019
• Study Completion (Actual): April 26, 2019

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: October 6, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Saracatinib
• Other Study ID Numbers: 1503015528