MDMA in Subjects With Moderate Hepatic Impairment and Subjects With Normal Hepatic Function

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is an open-label, single dose study evaluating the effect of moderate hepatic impairment in the pharmacokinetics of MDMA and its active metabolite, 3,4-methylene-dioxyamphetamine (MDA) in order to decide whether an adjustment to the dosage would be need for individuals with moderate hepatic function in comparison to individuals with normal liver function. Eight participants with moderate hepatic impairment and eight matched participants with normal hepatic function will take part in this study. All patients will be evaluated to see if they meet criteria for study participation, with screening including a physical examination including a 12-lead electrocardiogram (ECG) and questions about mental and physical health. Participants who meet study criteria will stay at the study site for three days. On Day 1, they will receive a single dose of 80 mg MDMA. For the next seven to eight hours, participants will have blood collected and will rate their mood and other experiences. They will stay at the study sight for two more days. Blood will be drawn twice on the second day and once on the third day, and they will have their heart function measured with ECG. Blood will be collected periodically during a 12-hour interval on the day of drug administration. Blood will also be drawn 24, 36, 48, 72 and 96 hours after MDMA administration. Participant mood and feelings or experiences on-drug (subjective effects) will be measured a half-hour, one, two, four, six, and seven hours after receiving MDMA. ECG will be performed every day at the same time upon enrollment (Day -4 or -3) and from the Day 1 (day of drug administration) to Day 5. Blood pressure, heart rate and body temperature on Day 1 through 5. Blood samples will be used to compute the peak or maximum amount of MDMA and MDA in blood (Cmax), the time until reaching peak MDMA or MDA (Tmax) and the area under curve (AUC), or actual degree of exposure to drug. The primary outcome measure will be AUC for MDMA. Finding out if there are differences in drug metabolism between people with normally functioning livers and people whose livers do not function normally will help researchers performing MDMA-assisted psychotherapy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Multidisciplinary Association for Psychedelic Studies
• Treatments: N-Methyl-3,4-methylenedioxyamphetamine

Criteria

Inclusion Criteria:

• Participants with moderate hepatic impairment (class B according to Child- Pugh's criteria).

• Participants with normal hepatic function: no clinically significant findings from medical history, physical examination, laboratory values within protocol defined parameters.

• Age 18 to 65 years.

• Weight > 45 kg

• Negative Carbohydrate Deficient Transferrin blood test at Screening and negative breathalyzer alcohol test prior to trial drug administration.

• Negative urine test for drugs of abuse at Screening and prior to trial drug administration.

• Able to comprehend and willing to sign an informed consent form.

Exclusion Criteria:

• Have a current psychiatric diagnosis.

• Are pregnant or nursing, or are women of child bearing potential who are not practicing an effective means of birth control.

• Have acute or exacerbating hepatitis, fluctuating or rapidly deteriorating hepatic function as indicated by widely varying or worsening of clinical and/or laboratory signs of hepatic impairment within 2 weeks.

• Have autoimmune liver disease; esophageal variceal bleeding within 6 months prior to screening, unless successfully treated with banding, or gastric varices.

• Have spontaneous bacterial peritonitis within 3 months prior to screening.

• Have a portosystemic shunt, organ transplant, Wilson's disease, cholestatic liver disease (e g, primary biliary cirrhosis or primary sclerosing cholangitis)

• Evidence or history of significant hematological, endocrine, cerebrovascular, cardiovascular (including controlled hyper-tension), coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of MDMA administration.

• For moderate hepatic impairment participants: have clinically significant laboratory findings except as related to hepatic impairment.

• For control participants only: have clinically significant laboratory results outside the normal limits, including AST >48 U/L, ALT > 55 U/L, GGT > 48 U/L, bilirubin > 1.2 mg/dL or hemoglobin < 12 g/dL.

• Have a history of any illness that, in the opinion of the Investigator, might confound the results of the trial or pose risk in administering the trial drug to the subject.

• Have any positive test for drugs of abuse and /or alcohol at screening.

• Have a history or presence of clinically significant abnormal 12-lead ECG or an ECG with QTc by Bazett's correction of > 450 ms in men, > 470 ms in women on the screening ECG.

• Have a PR interval > 240 ms, QRS > 110 ms or a history of prolongation of QT interval.

• Have mental incapacity, unwillingness or language barriers precluding adequate understanding or subject co-operation.

• Are unwilling to stay in the clinical unit for the required duration as per the protocol.

• Have a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.

• Have a known or suspected allergy to trial product or related products.