Studie účinnosti, bezpečnosti a snášenlivosti AVP-786 jako doplňkové terapie u pacientů s těžkou depresivní poruchou s nedostatečnou odpovědí na léčbu antidepresivy
Multicentrická, randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie fáze 2 k posouzení účinnosti, bezpečnosti a snášenlivosti AVP-786 (deuteriem modifikovaný dextromethorfan hydrobromid/chinidin sulfát) jako doplňkové léčby u pacientů s těžkou depresivní poruchou Nedostatečná odpověď na léčbu antidepresivy
The objectives of this 10-week study are to evaluate the efficacy, safety, and tolerability of AVP 786 as an adjunctive therapy compared with placebo in patients with major depressive disorder (MDD) who have shown an inadequate response to standard antidepressant treatment. A secondary objective of this study is to assess the pharmacokinetics (PK) of AVP-786 and potential correlations with pharmacodynamic effects.
Přehled studie
Postavení
Detailní popis
It is estimated that up to approximately 200 patients will participate in the study at approximately 30 enrolling centers in the US.
Eligible patients for this study must have MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria, and have shown an inadequate response to standard antidepressant treatment.
This is a multicenter, randomized, double-blind, placebo-controlled, study of 10 weeks duration.
Following screening procedures for assessment of inclusion and exclusion criteria, eligible patients will be randomized into the study. Study medication will be administered orally twice a day (BID) (1 capsule in the morning and 1 capsule in the evening, approximately 12 hours apart) throughout the treatment period.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Alabama
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Birmingham, Alabama, Spojené státy, 35294
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Birmingham, Alabama, Spojené státy, 35213
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California
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Bellflower, California, Spojené státy, 90706
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Costa Mesa, California, Spojené státy, 92626
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Garden Grove, California, Spojené státy, 92845
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Lomita, California, Spojené státy, 90717
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Oceanside, California, Spojené státy, 92056
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Riverside, California, Spojené státy, 92506
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Santa Ana, California, Spojené státy, 92706
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Sherman Oaks, California, Spojené státy, 91403
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Colorado
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Denver, Colorado, Spojené státy, 80239
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Florida
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Bradenton, Florida, Spojené státy, 34201
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Jacksonville, Florida, Spojené státy, 32256
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Miami, Florida, Spojené státy, 33155
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Orange City, Florida, Spojené státy, 32763
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Orlando, Florida, Spojené státy, 32801
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Georgia
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Decatur, Georgia, Spojené státy, 30030
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Illinois
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Hoffman Estates, Illinois, Spojené státy, 60169
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Indiana
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Valparaiso, Indiana, Spojené státy, 46383
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Maryland
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Baltimore, Maryland, Spojené státy, 21285
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Glen Burnie, Maryland, Spojené státy, 21061
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02131
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New York
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Brooklyn, New York, Spojené státy, 11241
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New York, New York, Spojené státy, 10003
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Staten Island, New York, Spojené státy, 10312
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Ohio
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Garfield Heights, Ohio, Spojené státy, 44125
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Oklahoma
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Oklahoma City, Oklahoma, Spojené státy, 73112
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Oklahoma City, Oklahoma, Spojené státy, 73103
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Tulsa, Oklahoma, Spojené státy, 74101
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Pennsylvania
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Philadelphia, Pennsylvania, Spojené státy, 19104
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Philadelphia, Pennsylvania, Spojené státy, 19139
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Utah
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Murray, Utah, Spojené státy, 84123
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Clinical diagnosis of major depressive episode ≤ 24 months in duration
- HAM-D17 score ≥ 20.
- Documented to not have a significant (25% or greater) change in QIDS-SR16 score between Screening and Baseline visits.
- Patients have been deemed to have an inadequate response (less than 50% symptom reduction) to at least 1 but no more than 3 adequate antidepressant trials during the current depressive episode.
- Patients must be receiving ongoing treatment with an adequate dose of antidepressants.
- Body Mass Index (BMI) of 18-35 kg/m².
Exclusion Criteria:
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History of myasthenia gravis.
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Have cardiovascular concerns such as:
- History of complete heart block, QT interval corrected for heart rate (QTc) prolongation, or torsades de pointes.
- QTc using the Fridericia's formula (QTcF) at screening > 450 msec for males and > 470 msec for females based on central review at the screening visit, unless due to ventricular pacing.
- Any family history of congenital QT interval prolongation syndrome.
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Known hypersensitivity/intolerance to DM, Q, opiate drugs (codeine, etc.), or any other ingredient of the study medication.
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Pose a current suicide risk, as evidenced by any of the following:
- It is the judgment of the investigator that the subject may be at risk for suicide.
- The subject is rated a "yes" to question 4 or question 5 on the Baseline C-SSRS, if the most recent episode occurred within the past 12 months.
- The subject has attempted suicide within the past 6 months
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Presence of any other current DSM-IV-TR Axis I disorders with the exception of: generalized anxiety disorder (GAD: 300.02), social anxiety disorder (300.23), dysthymic disorder (300.4), or specific phobia (300.29). Patients with co-morbid GAD, social anxiety disorder, or specific phobia are ineligible if the co-morbid condition is clinically unstable, or has been the primary focus of treatment within the 6 month period prior to screening
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Axis I diagnosis of:
- Delirium, dementia, amnestic, or other cognitive disorder;
- Schizophrenia or other psychotic disorder, based on the M.I.N.I.;
- Bipolar I or II disorder, based on the M.I.N.I.
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Clinically significant Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: AVP-786
Participants receive AVP-786 capsules, orally, using a protocol-defined dose-escalation regimen (up to AVP-786 34/4.75 [34 milligrams (mg) deuterated (d6)-dextromethorphan (hydrobromide)/4.75 mg of quinidine (sulfate)] twice daily [BID]), in Periods 1 and 2 up to Day 35 and Day 70, respectively. |
AVP-786 capsules administered orally. |
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Komparátor placeba: Placebo
Participants receive placebo, orally, in Periods 1 and 2 up to Day 35 and Day 70, respectively. |
Matching placebo capsules administered orally. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score
Časové okno: Visit 5 (Day 70) Week 10
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The MADRS consists of 10 items, each rated based on the structured interview. The dimensions assessed in the MADRS are as follows: 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts. Each item is rated on a scale from 0 to 6. The MADRS total score is the sum of the scores for the 10 dimensions and can range from 0 to 60, with higher scores indicating a higher severity of depression. |
Visit 5 (Day 70) Week 10
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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17-item Hamilton Rating Scale for Depression (HAM-D17)
Časové okno: Visit 5 (Day 70) Week 10
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The HAM-D is a clinician-rated scale that evaluates the level of depression. The HAM-D consists of 17 items (with scale in parentheses) such as Depressed Mood (0-4), Guilt (0-4), Suicide (0-4), Insomnia, initial (0-2), Insomnia, middle (0-2), Insomnia, late (0-2), Work and Interests (0-4), Psychomotor Retardation (0-4), Psychomotor Agitation (0-4), Anxiety, psychic (0-4), Anxiety, somatic (0-4), Gastrointestinal Symptoms (0-2), Somatic Symptoms, general (0-2), Sexual Interest (0-2), Hypochondriasis (0-4), Insight (0-2), and Weight Loss (0-2). Summed subscales are combined to compute a total score. Total score ranges from 0 to 52, with a higher score indicating worse condition. |
Visit 5 (Day 70) Week 10
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Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ)
Časové okno: Visit 5 (Day 70) Week 10
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The MGH ATRQ is given in this study to assess treatment resistance in depression. Participants are to provide information on the questionnaire about the dose level and duration for each medication that has been taken during their current episode/stage of depression. Participants are also to provide the medication that helped them the most and answer a question about the degree of improvement. |
Visit 5 (Day 70) Week 10
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16-item Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR16)
Časové okno: Visit 5 (Day 70) Week 10
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The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) is a patient-reported questionnaire used to assess the severity of depressive symptoms over the previous 7 days. The questionnaire assesses sleep, mood, appetite/weight, concentration, self-perception, suicidal thoughts, interest, energy, and psychomotor changes. Each item is scored from 0 to 3, with higher scores indicating greater symptom severity. The total score is calculated using a standard algorithm that sums the highest-rated item within selected symptom domains and individual domain scores, resulting in a total score ranging from 0 to 27, with higher scores indicating more severe depressive symptoms. |
Visit 5 (Day 70) Week 10
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Sheehan Disability Scale (SDS)
Časové okno: Visit 5 (Day 70) Week 10
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The participant is to assess how disruptive their depression symptoms have been on a 0 to 10 scale, as shown below: 0 Not at all, 1 to 3 Mildly, 4 to 6 Moderately, 7 to 9 Markedly, 10 Extremely. The 3 items will be summed to obtain a measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). Higher scores indicate worse conditions. |
Visit 5 (Day 70) Week 10
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Clinical Global Impression of Severity of Illness (CGI-S)
Časové okno: Visit 5 (Day 70) Week 10
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The CGI-S is clinician's assessment of the participant's illness at the time of the assessment. The CGI-S is scored according to the following 7-point scale, with a higher score indicating a higher severity of illness (0 = not assessed): 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = extremely ill. |
Visit 5 (Day 70) Week 10
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Clinical Global Impression of Change (CGI-C)
Časové okno: Visit 5 (Day 70) Week 10
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The CGI-C is clinician's assessment of the participant's change in illness at the time of the assessment, using the following 7-point scale (0 = not assessed): 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. A lower score indicates an improvement in illness. |
Visit 5 (Day 70) Week 10
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EuroQOL 5 Dimension 5 Level (EQ-5D-5L)
Časové okno: Visit 5 (Day 70) Week 10
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The EQ-5D-5L, a scale used to measure quality of life, is divided into 2 parts, the descriptive system and the visual analog scale (VAS), reported as separate scores. The descriptive system is divided into five categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. For each category, the participant selects the one statement that best describes their health on the day of assessment. Each category is scored on a 5-point scale(1=no problems to 5=extreme problems or inability to perform the activity) [e.g., for mobility: 1 = no problems walking and 5 = unable to walk]. Missing values for a given category are imputed with a value of 9 and are excluded from the summary for that category. Higher scores for each category= worse health condition. The VAS is a 0 (worst health you can imagine) to 100 (best health you can imagine) vertical scale, where the participant places an X on the scale where they feel their health is today and then writes the number. |
Visit 5 (Day 70) Week 10
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Patient Global Impression of Change (PGIC)
Časové okno: Visit 5 (Day 70) Week 10
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The PGI-C asks the participant to rate their overall impression of change in their depression symptoms from the time of study entry to the present. The PGI-C is scored on a 7-point scale, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Higher scores indicate worsening of depression symptoms. |
Visit 5 (Day 70) Week 10
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7-item Generalized Anxiety Disorder (GAD-7)
Časové okno: Visit 5 (Day 70) Week 10
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The GAD-7 is a self-reported questionnaire used to assess symptoms of generalized anxiety disorder. It consists of 7 questions evaluating feelings of nervousness or anxiety, inability to stop or control worrying, excessive worrying, trouble relaxing, restlessness, irritability, and fear that something awful might happen. Each item is scored on a 4-point scale, where 0 = not at all, 1 = several days, 2 = more than half the days, and 3 = nearly every day. The scores for all seven items are summed to produce a total score ranging from 0 to 21, with higher scores indicating greater severity of anxiety symptoms. |
Visit 5 (Day 70) Week 10
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Spolupracovníci a vyšetřovatelé
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhadovaný)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 14-AVP-786-201
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Časový rámec sdílení IPD
Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
Kritéria přístupu pro sdílení IPD
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
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