NCT04506905已完成1 期
A 2-Part Randomized Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Alternate MK-8189 Titration Regimens in Young Adult Participants With Schizophrenia and to Evaluate the Safety, Tolerability and Pharmacokinetics of MK-8189 in Elderly Participants With Schizophrenia and Healthy Elderly
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 12
- 主要终点
- Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE)
研究概览
简要总结
This is a randomized, double-blind, 2-part clinical study of the safety, tolerability and pharmacokinetics of alternate elpipodect titration regimens. Part 1 assessed multiple dose once-daily titration regimens of elpipodect in young adult participants with schizophrenia. Part 2 assessed multiple once-daily doses of elpipodect in elderly participants with schizophrenia and healthy elderly participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Has a body mass index (BMI) ≤40 kg/m2
- •Has no clinically significant abnormality on 12-lead safety electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to randomization
- •Has a normal resting blood pressure (BP: systolic BP is ≥90 millimeter of mercury [mmHg] and ≤140 mmHg; diastolic BP is ≥60 mmHg and ≤90 mmHg) and normal resting heart rate (≥45 beats per minute [bpm] and ≤100 bpm) in the semirecumbent position at the prestudy (screening) visit and/or prior to randomization. Repeat evaluations may be done if the values for a participant are, per investigator discretion, minimally outside the designated range. Participants may be included if values are outside the normal range but considered not clinically significant per investigator discretion
- •Participants with schizophrenia only: Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria with the onset of the first episode being no less than 2 years prior to screening and monotherapy with antipsychotics for treatment should be indicated
- •Participants with schizophrenia only: Has a total Brief Psychiatric Rating Scale (BPRS) score of <48 with a BPRS score <4 for #10 (hostility) and #14 (uncooperativeness) at the screening visit
- •Participants with schizophrenia only: Is in the nonacute phase of their illness and clinically stable for 3 months prior to screening as demonstrated by the following: 1) no clinically significant change in dose of prescribed antipsychotic medication, or clinically significant change in antipsychotic medication to treat symptoms of schizophrenia for 2 months prior to screening 2) no increase in level of psychiatric care due to worsening of symptoms of schizophrenia for 3 months prior to screening
- •Participants with schizophrenia only: Has a history of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia
- •Participants with schizophrenia only: Has a stable living situation
- •Participants with hypothyroidism, diabetes, high BP, chronic respiratory conditions or other mild forms of these medical conditions could be considered as candidates for study enrollment if their condition is stable
- •Has regular bowel movements
- •Participants with schizophrenia only: Is able to discontinue the use of all antipsychotic medication at least 5 days prior to the start of the treatment period and during the study period
- •Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 14 days after the last dose of study intervention
排除标准
- •Is a WOCBP who has a positive urine pregnancy test within 48 hours before the first dose of study intervention
- •Participants with schizophrenia only: Has evidence or history of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria within 1 month of screening
- •Has evidence or history of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria within 1 month of screening
- •Has evidence or history of mental retardation, borderline personality disorder, anxiety disorder, or organic brain syndrome
- •Has a history of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia
- •Has a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse
- •Has a DSM-5 defined substance use disorder within 3 months of screening
- •Has a history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures
- •Has an untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cardiovascular, hematological, immunological or cerebrovascular disease, malignancy, allergic disease or other chronic and/or degenerative process at screening
- •Has any clinically significant abnormal laboratory, vital sign (VS), physical examination, or 12-lead safety ECG findings at screening or changes from baseline parameters or, in the opinion of the investigator, would make the participant inappropriate for entry into this study
- •Has a history of cancer with following exceptions: 1) Adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study, in the opinion of the investigator and with agreement of the Sponsor
- •Has a clinically significant history or presence of sick sinus syndrome, first, second, or third-degree AV block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged corrected QT (QTc) interval, or conduction abnormalities
- •Has history of repeated or frequent syncope, vasovagal episodes, or epileptic seizures
- •Has a family history of sudden death
- •Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study
- •For Part 2 participants only: Participant has an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 based on the modification of diet in renal disease (MDRD). Participants who have an eGFR or measured creatinine clearance of up to10% below of either 60 milliliter/minute [mL/min] (for creatinine clearance) or 60 mL/min/1.73m2 (for eGFR) may be enrolled in the study at the discretion of the investigator
- •Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
- •Is positive for Hepatitis B surface antigen, Hepatitis C antibodies or HIV
- •Had major surgery, donated or lost 1 unit of blood within 4 weeks prior to the prestudy (screening) visit
- •Healthy participants only: Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years (participants who have had situational depression may be enrolled in the study at investigator's discretion)
- •Participants with schizophrenia only: Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator
- •Healthy participants only: Is at imminent risk of self-harm, based on clinical interview and responses on the CSSRS, or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or in the past 5 years or suicidal behavior in their lifetime
- •Has received treatment with clozapine for schizophrenia or treatment with monoamine oxidase inhibitors within 3 months of screening or cariprazine within 2 months of screening
- •Has received a parenteral depot antipsychotic medication within 3 months of screening
- •Is unable to refrain from the use of co-medication with a moderate or strong inhibiting or inducing effect on cytochrome (CYP3A) and/or cytochrome (CYP2C9) beginning approximately 2 weeks or 5 half-lives, whichever is longer, prior to administration of the initial dose of trial drug and throughout the trial or is unable to refrain from the use of sensitive substrates of cytochrome (CYP2B6)
- •Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
- •Has been in incarceration or imprisonment within three months prior to screening
- •Is a current smoker (healthy participants only) or is a smoker (participants with schizophrenia only) that does not agree to follow the smoking restrictions as defined by the clinical research unit (CRU)
- •Consumes greater than 3 glasses of alcoholic beverages per day. Participants who consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator
- •Consumes excessive amounts, defined as greater than 6 servings of caffeinated beverages per day
- •Is a regular user of cannabis, any illicit drugs or has a history of drug abuse within approximately 3 years
- •Presents any concern by the investigator regarding safe participation in the study or for any other reason the investigator considers the participant inappropriate for participation in the study
- •Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study
研究组 & 干预措施
Part 1 (Panels A, B, C) Placebo
Placebo Comparator
Oral tablets of dose-matched placebo to total daily dose of elpipodect.
干预措施: Placebo (Drug)
Part 2 (Panels D, E, F, G) Placebo
Placebo Comparator
Oral tablets of dose-matched placebo to total daily dose of elpipodect.
干预措施: Placebo (Drug)
Part 1 (Panel A) Elpipodect
Experimental
Young adult participants with schizophrenia receive elpipodect titrated from 16 mg to 24 mg once daily (QD), orally, over a course of 7-day treatment.
干预措施: Elpipodect (Drug)
Part 1 (Panel B) Elpipodect
Experimental
Young adult participants with schizophrenia receive elpipodect titrated up to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panel.
干预措施: Elpipodect (Drug)
Part 1 (Panel C) Elpipodect
Experimental
Young adult participants with schizophrenia receive elpipodect titrated from 8 mg to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
干预措施: Elpipodect (Drug)
Part 2 (Panel D) Elpipodect
Experimental
Elderly adult participants with schizophrenia receive elpipodect titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
干预措施: Elpipodect (Drug)
Part 2 (Panel E) Elpipodect
Experimental
Elderly adult participants with schizophrenia receive elpipodect titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
干预措施: Elpipodect (Drug)
Part 2 (Panel F) Elpipodect
Experimental
Healthy elderly adult participants receive elpipodect titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
干预措施: Elpipodect (Drug)
Part 2 (Panel G) Elpipodect
Experimental
Healthy elderly adult participants receive elpipodect titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
干预措施: Elpipodect (Drug)
结局指标
主要结局
Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 27 days
The number of participants with ≥1 AE is reported. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE
时间窗: Up to approximately 27 days
The number of participants discontinuing from study treatment due to ≥1 AE is reported. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189(Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Concentration 24 Hours Postdose (C24) of MK-8189(Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Maximum Plasma Concentration (Cmax) of MK-8189(Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Time to Maximum Concentration (Tmax) of MK-8189(Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Clearance (CL/F) of MK-8189(Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Apparent Terminal Half-life (t½) of MK-8189(Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Volume of Distribution (Vd/F) of MK-8189(Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: AUC0-24 of MK-8189(Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: C24 of MK-8189(Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Cmax of MK-8189(Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Tmax of MK-8189(Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: CL/F of MK-8189(Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: t½ of MK-8189(Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Vd/F of MK-8189(Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose)
研究者
研究点 (12)
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