抗うつ薬治療に対する反応が不十分な大うつ病性障害患者における補助療法としての AVP-786 の有効性、安全性、忍容性に関する研究
AVP-786 (重水素修飾デキストロメトルファン臭化水素酸塩/硫酸キニジン) の有効性、安全性、忍容性を評価する第 2 相、多施設、無作為化、二重盲検、プラセボ対照試験。抗うつ薬治療に対する不十分な反応
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.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
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.
研究の種類
研究の種類
入学 (実際)
入学
段階
段階
- フェーズ2
連絡先と場所
研究場所
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Alabama
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Birmingham、Alabama、アメリカ、35294
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Birmingham、Alabama、アメリカ、35213
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California
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Bellflower、California、アメリカ、90706
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Costa Mesa、California、アメリカ、92626
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Garden Grove、California、アメリカ、92845
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Lomita、California、アメリカ、90717
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Oceanside、California、アメリカ、92056
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Riverside、California、アメリカ、92506
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Santa Ana、California、アメリカ、92706
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Sherman Oaks、California、アメリカ、91403
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Colorado
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Denver、Colorado、アメリカ、80239
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Florida
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Bradenton、Florida、アメリカ、34201
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Jacksonville、Florida、アメリカ、32256
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Miami、Florida、アメリカ、33155
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Orange City、Florida、アメリカ、32763
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Orlando、Florida、アメリカ、32801
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Georgia
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Decatur、Georgia、アメリカ、30030
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Illinois
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Hoffman Estates、Illinois、アメリカ、60169
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Indiana
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Valparaiso、Indiana、アメリカ、46383
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Maryland
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Baltimore、Maryland、アメリカ、21285
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Glen Burnie、Maryland、アメリカ、21061
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Massachusetts
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Boston、Massachusetts、アメリカ、02131
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New York
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Brooklyn、New York、アメリカ、11241
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New York、New York、アメリカ、10003
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Staten Island、New York、アメリカ、10312
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Ohio
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Garfield Heights、Ohio、アメリカ、44125
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73112
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Oklahoma City、Oklahoma、アメリカ、73103
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Tulsa、Oklahoma、アメリカ、74101
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
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Philadelphia、Pennsylvania、アメリカ、19139
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Utah
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Murray、Utah、アメリカ、84123
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参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
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実験的：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. |
|
プラセボコンパレーター：Placebo
Participants receive placebo, orally, in Periods 1 and 2 up to Day 35 and Day 70, respectively. |
Matching placebo capsules administered orally. |
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score
時間枠：Visit 5 (Day 70) Week 10
|
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
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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17-item Hamilton Rating Scale for Depression (HAM-D17)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：Visit 5 (Day 70) Week 10
|
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
|
協力者と研究者
スポンサー
スポンサー
研究記録日
主要日程の研究
研究開始 (実際)
研究開始
一次修了 (実際)
一次修了
研究の完了 (実際)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (推定)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
その他の研究ID番号
- 14-AVP-786-201
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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.
IPD 共有時間枠
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.
IPD 共有アクセス基準
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。