ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Purpose
The goal of this clinical trial is to learn if ACP-211 can help treat adults with major depressive disorder (MDD) who have not improved with antidepressant therapy (ADT), including those with treatment resistant depression (TRD). The main questions the study aims to answer are: - Does ACP-211 work better than a placebo (a look-alike capsule with no medicine) to reduce symptoms of depression? - What adverse events do participants have when taking ACP-211?
Conditions
- Major Depressive Disorder (MDD)
- Depressive Disorder, Treatment-Resistant
Eligibility
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male or female ≥18 and ≤65 years of age at Screening - Clinical diagnosis of MDD per DSM-5, confirmed by the MINI during Screening - Willing to abstain from prohibited drugs or substances from Screening through the end of the study. Benzodiazepines, non-benzodiazepine sleep aids, and benztropine are prohibited from 12 hours before, until 24 hours after, each study drug administration. - Willing to abstain from alcohol within 24 hours before and after study drug administration - If female, the participant must either: - Be of non-childbearing potential (defined as either at least 6 months surgically sterilized or at least 1 year postmenopausal), OR - Have a male partner who has had a vasectomy, OR - Beginning at least 28 days prior to the first dose of study drug until 28 days after the last dose, use a combination of two nonhormonal methods of contraception, such as: - An IUD and a barrier method (e.g., condom, diaphragm) plus spermicide, - Or a barrier method with her male partner using a condom. - Females must have a negative serum hCG pregnancy test at Screening and a negative urine pregnancy test at Baseline. - If male, the participant must: - Use a condom (even if vasectomized) from Screening until 90 days after the last dose. - Agree to not donate sperm for the duration of the study and until 90 days after the last dose. - Inadequate response to ≥2 antidepressants (excluding MAOIs) with ≥1 inadequate response to antidepressant confirmed in the current episode of depression - Includes patients who have had a partial response to antidepressants and those who have minimal or no response - MGH ATRQ will be used to assess ADT response during the current episode - Prior medication history will be used to determine ADT response in prior episode(s) - Treated during the current major depressive episode with any regulatory approved antidepressant(s) at a minimally effective or higher dose for ≥8 weeks with the same stable dose for ≥4 weeks prior to the MGH ATRQ assessment at Screening - Detectable blood level of a prescribed SSRI/SNRI/augmentation AP during Screening - If clinically appropriate, willing to discontinue antidepressant and augmentation medications ≥5 half-lives prior to Baseline. No antidepressants or augmentation medications are allowed to be taken any time within 14 days prior to Baseline. - MADRS total score ≥28 at Screening and Baseline - CGI-S score ≥4 (moderately ill or worse) for depression at Screening and Baseline - QIDS-SR16 score ≥16 at Screening and Baseline - On all dosing days, participants must: - Remain at the clinical site at least 4 hours postdose. - Be accompanied upon discharge. - Not to drive or operate heavy machinery for 24 hours postdose.
Exclusion Criteria
- Diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder, and persistent depressive disorder - Substance use disorders within the last 6 months prior to Screening (excluding caffeine or nicotine) - Evidence of delirium or unstable medical conditions (e.g., neurological, cardiovascular, cancer) - Suicidal at Screening or Baseline defined as: - "Yes" to C-SSRS questions 4 or 5 (current or over the last 6 months); OR - Attempted suicide within 1 year prior to Visit 1 (Screening); OR - Actively suicidal in the Investigator's judgment - History of schizophrenia, psychotic disorders, MDD with psychotic features, bipolar I or II - Being treated or require treatment for PTSD, acute stress disorder, panic disorder, or OCD - History of neuroleptic malignant syndrome or serotonin syndrome - History of epilepsy (except single febrile seizure in infancy) - History of non-response to ADT during the induction phase, including ketamine and/or esketamine or other oral antidepressants (≥2 but ≤5 different antidepressant drugs) - Allergy or sensitivity to ketamine or esketamine - History of myocardial infarction, unstable angina, acute coronary syndrome, or cerebrovascular accident - History of uncontrolled hypertension or hypertensive crisis, congestive heart failure > NYHA Class II , Grade II or greater angina pectoris (by Canadian Cardiovascular Society Angina Grading Scale), sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes, syncope due to an arrhythmia, an implantable cardiac defibrillator, or severe symptomatic hypotension - Personal or family history of long QT syndrome or sudden cardiac death - Atrial fibrillation unless adequately anti-coagulated - History of a positive hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV test - One or more clinical laboratory test value(s) at Screening outside the limits specified below: - Hemoglobin <12 g/dL (men) or <11 g/dL (women) - AST or ALT >2× ULN - Total bilirubin >25.7 μmol/L (1.5 mg/dL), unless Gilbert's syndrome is documented - Serum creatinine >2× ULN - Creatine kinase >1000 U/L - Severe renal impairment at Screening (eGFR of 30 mL/min) - History of recurrent urinary tract infections, urinary tract neoplasm or benign enlargement and urinary retention - Hypothyroidism at Screening (unless TSH is abnormal and reflex free T4 is normal) - Unstable diabetes or HbA1c >8% at Screening - Abnormal ECG results at Screening or Baseline - Heart rate <50 beats per minute, not explained by regular exercise or medication - BMI <18.5 or >35 kg/m2 at Screening or unintentional weight loss (i.e., ≥7%) over past 6 months - Positive urine drug test for an illicit drug or cannabis at Screening or positive urine drug dipstick test result at Baseline - Received electroconvulsive therapy (at least 7 treatments), transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation in the current episode of depression - Received new-onset psychotherapy or had a change in the intensity of psychotherapy within 8 weeks prior to Screening - Participated in a noninterventional study or clinical trial within 30 days or 5 half-lives, whichever is longer, of Baseline - Employee or family member of an employee of Acadia Pharmaceuticals Inc. - Judged to be inappropriate for the study, including if the participant is a danger to self or others (e.g., occupations in mass transportation or operating heavy machinery) Additional inclusion/exclusion criteria apply. Participants will be evaluated at Screening to ensure that all criteria for study participation are met.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental ACP-211 600 mg |
ACP-211 600 mg, administered orally twice weekly |
|
|
Experimental ACP-211 300 mg |
ACP-211 300 mg, administered orally twice weekly |
|
|
Placebo Comparator Placebo |
Matching placebo, administered orally twice weekly |
|
Recruiting Locations
Clinical Neuroscience Solutions
Orlando 4167147, Florida 4155751 32819
Orlando 4167147, Florida 4155751 32819
CenExel
Marlton 4502911, New Jersey 5101760 08053
Marlton 4502911, New Jersey 5101760 08053
More Details
- Status
- Recruiting
- Sponsor
- ACADIA Pharmaceuticals Inc.