| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Negative Symptoms of Schizophrenia |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLGT |
| E.1.2 | Classification code | 10039628 |
| E.1.2 | Term | Schizophrenia and other psychotic disorders |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of 2 fixed doses (32 mg and 64 mg) of MIN-101 compared to placebo in improving the negative symptoms of schizophrenia as measured by the change in the Positive and Negative Syndrome Scale (PANSS) Marder negative symptoms factor score (NSFS) over 12 weeks of double-blind treatment. |
|
| E.2.2 | Secondary objectives of the trial |
Key Secondary
To assess the effect of MIN-101 compared to placebo on the Personal and Social Performance (PSP) total score, over 12 weeks of double-blind treatment.
Secondary
To assess the effect of MIN-101 compared to placebo over 12 weeks of double-blind treatment on:
• Clinical Global Impression of Severity (CGI-S).
• Safety and tolerability.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each potential patient must satisfy all the following criteria to be enrolled in the study:
1. Patient and patient's legal representative, if applicable, provided informed consent prior to the initiation of any study related procedures, and the patient is judged by the investigator as being capable of understanding the study requirements.
2. Male or female patient, 18 to 55 years of age, inclusive, and body mass index (BMI) < 35 kg/m2 at Screening.
3. Patient meets the diagnostic criteria for schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), as established by a full psychiatric interview in conjunction with the Mini International Neuropsychiatric Interview (MINI).
4. Has a caregiver or family member or health care personnel who can provide information towards assessment and support the patient in terms of compliance with the protocol. The caregiver must have contacts with the patient frequently and is not expected to change during the trial.
5. Documented diagnosis of schizophrenia for at least 1 year before screening into the trial.
6. Patient is stable in terms of both positive and negative symptoms of schizophrenia over the last 6 months according to his or her clinician and/or based on documentation in the clinical chart or medical records. Patients with or without positive symptoms are allowed if these symptoms are stable for the last 6 months and the patients do not meet exclusion criterion # 2.
7. Patient is currently an outpatient and has not been hospitalized for the last 6 months for acute exacerbation or symptoms worsening. Patients hospitalized for any time period during the last 6 months for social reasons or are currently hospitalized for social reasons can be included only with Sponsor's Responsible Medical Officer's approval (in addition for Ukraine only, the following criteria must be fulfilled: the patient has permanent place of residence, is legally capable, and has a caregiver [see inclusion criterion # 4]). The social reasons must be documented in the electronic case report form (eCRF)
8. Patient with a score of > 20 on the PANSS negative subscore (the original PANSS scale [Sum of N1+N2+N3+N4+N5+N6+N7]) at Screening (Visit 1) and Baseline (Visit 3) AND < 4 points absolute difference between the 2 visits.
9. Patients can be on any psychotropic before the trial if the psychotropics can be discontinued at the beginning of the washout phase without risking the patient’s clinical status or safety.
10. No history of violence against self or others during the last 1 year.
11. Female patient who are not of childbearing potential, defined as women who are post- menopausal (defined as spontaneous amenorrhoea for at least 1 year or spontaneous amenorrhoea for at least 6 months confirmed by follicle stimulating hormone result of ≥ 40 IU/mL) or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
12. Female patient, if of childbearing potential, must test negative for pregnancy and must be using a double barrier contraceptive method.
13. Patient must be extensive (normal) metabolizers for P450 CYP 2D6, defined as a subject that has at least one functional allele (e.g., *1, or *2), as determined by study-specific genotyping test before the first drug dose is administered.
14. Patient and the caregiver are considered by the investigator to be reliable and likely to cooperate with the assessment procedures.
|
|
| E.4 | Principal exclusion criteria |
Any potential patient who meets any of the following criteria will be excluded from participating in the study:
1. Current major depressive disorder, bipolar disorder, panic disorder, obsessive compulsive disorder, or intellectual disability (intellectual developmental disorder diagnosed by age 14).
2. Patient with PANSS item score of > 4 on:
• P4 Excitement/Hyperactivity
• P6 Suspiciousness/persecution
• P7 Hostility
• G8 Uncooperativeness
• G14 Poor impulse control
3. A CDSS total score > 6.
4. A score of ≥ 2 on any 2 of items 1, 2, or 3, or a score of ≥ 3 on item 4 of the Barnes Akathisia Rating Scale (BARS).
5. Patient’s condition is due to direct physiological effects of a substance (e.g., a drug of abuse, or medication) or a general medical condition.
6. Has a current or recent history of serious suicidal behavior within the past 1 year.
7. Patient has a history of substance use disorder within 3 months of the Screening visit (excluding caffeine and cigarette smoking).
8. Positive urine drug screen for drugs of abuse (cocaine, methadone, amphetamines, cannabinoids, opiates, benzodiazepines, and barbiturates), tricyclic antidepressants (TCA), and alcohol (except for prescription benzodiazepines).
9. Patient who cannot be discontinued from psychotropics other than those allowed.
10. Patient who received clozapine within 6 months of the Screening visit except when used for insomnia at doses ≤ 100 mg per day.
11. Patient receiving treatment with long-acting or depot antipsychotic medication unless his/her next scheduled dose will occur during the protocol Screening period and can be omitted to allow for sufficient washout before receiving the study drug.
12. Patient with a history of significant other major or unstable neurological, neurosurgical (e.g., head trauma), metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, metabolic, gastrointestinal, or urological disorder.
13. Patient with a history of seizures (patient with a history of a single childhood febrile seizure may be enrolled in this study).
14. Patient who has had electroconvulsive therapy (ECT), vagal nerve stimulation (VNS), or repetitive trans-cranial magnetic stimulation (r-TMS) within the 6 months prior to the Screening visit or who are scheduled for ECT, VNS, or r-TMS at any time during the study.
15. Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
16. Current systemic infection (e.g., Hepatitis B, Hepatitis C, human immunodeficiency virus [HIV], tuberculosis). Patients with positive Hepatitis B core antibody test and negative Hepatitis B Surface Antigen (HBsAg) may be included in the study if aminotransferase levels (alanine aminotransferase/ serum glutamic pyruvic transaminase [ALT/SGPT] and aspartate aminotransferase/ serum glutamic oxaloacetic transaminase [AST/SGOT]) do not exceed 2 times upper limit of normal (ULN).
17. Patient who requires or may require concomitant treatment with any other medication likely to increase QT interval (e.g., paroxetine, fluoxetine, duloxetine, amiodarone).
18. Patient who requires medication inhibiting CYP 2D6 or CYP 3A4.
19. Patient with a clinically significant ECG abnormality that could be a safety issue in the study, including QT interval value corrected for heart rate using the Fridericia’s formula (QTcF) > 430 msec for males and > 450 msec for females.
20. Patient with a history of myocardial infarction based on medical history or ECG findings at Screening.
21. Familial or personal history of long QT syndrome or with additional risk factors for Torsade de Pointes.
22. Patient whose safety laboratory results show one or more of the following: potassium <3.4 mmol/L, or calcium <2.07 mmol/L, or
magnesium <0.70 mmol/L.
23. Patients with unexplained syncope.
24. Woman of child-bearing potential, or man, who are unwilling or unable to use accepted methods of birth control.
25. Woman with a positive pregnancy test, is lactating, or is planning to become pregnant during the study.
26. Patient who participated in another clinical study within 3 months prior to Screening, or received MIN-101 previously, or has previously participated in > 2 clinical studies with experimental medication within the past 2 years (previous participation in 3 clinical studies with experimental medication will require approval of the sponsor before eligibility is determined). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from Baseline in the Positive and Negative Syndrome Scale (PANSS) Marder negative symptoms factor score (NSFS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Efficacy will be evaluated based on the change from Baseline in PANSS NSFS after 12 weeks of treatment or at early withdrawal. |
|
| E.5.2 | Secondary end point(s) |
End point for Key Secondary:
- Change from Baseline in the PSP Total score
End point for Secondary
- Change from Baseline in the CGI-S score
- Safety assessments, including adverse events, laboratory values, ECG, vital signs, physical exam, Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Simpson-Angus Scale (SAS) and the Sheehan Suicidality Tracking Scale (Sheehan-STS). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• PSP at Baseline and WKS 4, 8, 12, and at WKS 16, 24, 32, 40, 48, and 52 (or early withdrawal).
• CGI-S at Baseline and WKS 2, 4, 8, 12, and at WKS 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 54 (EOS or early withdrawal).
• Adverse events, laboratory values, ECG, vitals signs, physical exam, AIMS, BARS, Simpson-Angus Scale (SAS) and Sheehan-STS: throughout the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Georgia |
| Israel |
| Moldova, Republic of |
| Poland |
| Romania |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| A patient will be considered to have completed the study if he or she has completed all scheduled assessments through Week 12. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 20 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
Print
