To evaluate whether AFQ056 can have a beneficial effect by reducing cocaine use in Cocaine Use Disorder (CUD) patients and also guide the design of future clinical trials with mGlu5 antagonists in substance use disorders.
- Conditions
- Cocaine Use Disorder according to DSM 5MedDRA version: 20.0 Level: LLT Classification code 10009815 Term: Cocaine addiction System Organ Class: 100000173266Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2017-000736-33-ES
- Lead Sponsor
- ovartis Farmacéutica S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 60
1) Understand the study procedures and provide written informed consent before any assessment is performed.
2) Male and female subjects, 18 to 65 years of age (inclusive) and diagnosed with Cocaine Use Disorder according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Ed.).
3) Must use cocaine through snorting (intranasally), as primary route of administration.
4) Recent cocaine use confirmed by positive urine screen for 1 or more benzoylecgonine (BE)
5) Must be seeking treatment for cocaine dependence and have a desire to reduce or cease cocaine use as per goals assessed at baseline.
6) Must be abstinent from cocaine use for at least 3 days preceding 1st dosing (Day 1) as assessed by self-report TLFB and two *urinalysis samples at baseline.
* difference in BE level between two baseline's samples must decrease
7) Must be in good health as determined by medical history, physical examination, at screening
8) At screening, and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) must be within the acceptable ranges by the investigator considering the cocaine's increasing effect on pulse rate in order for the subject to qualify. Investigator may be guided to use the below ranges:
- systolic blood pressure, 90-150 mmHg
- diastolic blood pressure, 50-90 mmHg
Three readings are acceptable. At least the one of three reading must be within the acceptable ranges.
9) Patients must be able to:
- communicate well verbally with the Investigator and to understand written instructions
- verbalize a willingness to complete all study procedures
- verbally acknowledge that she/he will be able to attend each scheduled visit, and that she/he does not have any already scheduled events or activities that may substantially interfere with study participation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
1) History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes.
2) Has current diagnosis of Substance Use Disorder (according to the DSM 5) on alcohol, cannabis or other stimulants, except cocaine.
3) Meets current or lifetime DSM 5 criteria for schizophrenia or any psychotic disorder, or organic mental disorder.
4) Have current treatment for Substance Use Disorder (e.g.: disulfiram, acamprosate, methyl phenidate, modafinil, topiramate, immediate release dexamfetamine, or baclofen).
5) Requires treatment with any psychoactive medications, including any anti-seizure medications (with an exception of medications used for short-term treatment of insomnia)
6) Use of other investigational drugs at the time of screening, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
7) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
8) Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing and for 30 days after last dosing of study medication.
9) History of Porphyria.
10) History or presence of malignancy of any organ system, (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
11) Have a history of any illness, condition, and use of medications that in the opinion of the investigator or designee might confound the results of the study or pose additional risk in administering the investigational agents to the subject or preclude successful completion of the study
12) Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
13) Current or/and previous treatment with concomitant medications that are strong or moderate inducers/inhibitors of CYP3A4 (e.g., Clarithromycin, ketoconazole, ritonavir, etc.)
14) Concomitant use of agents known to prolong the QT interval unless these can be permanently discontinued for the duration of study.
15) History or current diagnosis of ECG abnormalities, at screening or baseline, indicating significant risk of safety for subjects participating in the study
16) Known history or presence of cardiovascular or cerebrovascular disease such as: angina pectoris, myocardial infarction, stroke, transient ischemic attack, peripheral vascular disease.
17) History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
18) Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
19) Score yes” on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or yes” on any item of the Suicidal Behavior section, except for the Non-Suicidal Self-Injurious Behavior” (item
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate treatment effect of 98-day AFQ056 administration in reducing cocaine use.;Primary end point(s): Proportion of cocaine use days by TLFB cocaine self-report.;Timepoint(s) of evaluation of this end point: 98 days.;<br> Secondary Objective: To assess the effects of 98-day AFQ056 administration versus placebo on:<br> a) other measures of cocaine use<br> b) alcohol use<br> To assess the safety and tolerability of multiple bid oral doses of AFQ056.<br> To evaluate the pharmacokinetics of AFQ056.<br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): a) Urinalysis (cocaine Benzoylecgonine (BE)<br> b)TLFB alcohol self-report; urinalysis (Ethyl Glucuronide (EtG))<br> c) Vital signs, ECG parameters, clinical safety laboratory parameters (chemistry/hematology/urinalysis), (serious) adverse events reporting, suicidal ideation (Columbia Suicide Severity Rating Scale (C-SSRS)<br> d) AFQ056 plasma concentrations (pre- and post-dose levels).<br> ;Timepoint(s) of evaluation of this end point: 98 days.