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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21AA030097-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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The goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (AUD). The main questions it aims to answer are:
Participants will be randomized to a treatment group (SUV or placebo) and protocol arm, electromyography (EMG) only or EMG+functional magnetic resonance imaging (fMRI). Participants will be asked to complete the following:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. |
|
| Suvorexant Treatment | Experimental | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Suvorexant | Drug | This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. |
| Measure | Description | Time Frame |
|---|---|---|
| Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant | Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat. U-threat residual scores were calculated for the baseline session and the acute challenge. | Change from baseline to 2 hours post-ingestion of an acute dose of suvorexant. |
| Startle Eyeblink Electromyographic (EMG) Response to Stress With Daily Use of Suvorexant. | Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat. | Change from baseline to post-treatment, up to 2 months. |
| Percentage of Heavy Drinking Days During Daily Use of Suvorexant. | Percentage of heavy drinking days (PHDD) was calculated each week for all four weeks of the trial. A heavy drinking day was defined using NIH criteria: 5+ drinks for males and 4+ drinks for females in a single day. We conducted a multilevel mixed model with PHDD from week 1 to 4 as the within-subjects variable and treatment arm as the between subjects variable. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Neural Activation During Unpredictable Stress Anticipation Following Daily Use of Suvorexant. | Activation parameter estimates (arbitrary units) were extracted from anatomical bilateral aINS masks for each individual, pre and post treatment. Specifically, activation parameter estimates were extracted from anticipation of unpredictable threat > anticipation of no-threat individual contrast maps for each scanning session. Greater values reflect greater activation in the bilateral insula during the anticipation of unpredictable threat. A repeated measures analysis of variance was used to test the session (time 1 vs. time 2) by treatment arm interaction on bilateral aINS activation during unpredictable threat. Significance was set at p <.05 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Ohio State University | Columbus | Ohio | 43210 | United States |
De-identified data, including fMRI, startle eyeblink, and behavior, from this project will be submitted to the NIAAA Data Archive (NDA) at the subject level along with appropriate supporting documentation to enable efficient use of the data by the research community. We will follow instructions as discussed in the NIAAA Data Archive Data Sharing Terms and Conditions.
We will follow the two-tier procedure described in the guidelines:
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The data, as outlined above, will be submitted to the NIAAA Data Archive biannually per NIAAA requirements throughout the duration of the study.
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Of 81 enrolled participants, 64 participants were randomized to treatment.
Participants were recruited via print advertisements, word-of-mouth referrals, and internet postings throughout Columbus and the surrounding area between November 2022 and June 2024. The first participant was enrolled on November 29th, 2022 and the last participant was enrolled in June 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo+EMG Only | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Placebo: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG only). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. |
| FG001 | Suvorexant+EMG Only | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. Suvorexant: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG only). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. |
| FG002 | Placebo+fMRI+EMG | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Placebo: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG +fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. |
| FG003 | Suvorexant+fMRI+EMG | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. Suvorexant: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo + EMG Only | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Placebo: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG only). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant | Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat. U-threat residual scores were calculated for the baseline session and the acute challenge. | A total of 57 participants were included. Missing data was due to attrition, poor quality startle eyeblink data, or technical errors during startle data collection. | Posted | Mean | Standard Error | Standardized residual scores | Change from baseline to 2 hours post-ingestion of an acute dose of suvorexant. |
2 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo + EMG Only | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Placebo: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG only). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abnormal dreams | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Stephanie Gorka | The Ohio State University | 614-366-1027 | stephanie.gorka@osumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 17, 2024 | Jun 4, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C551624 | suvorexant |
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|
| Placebo | Other | This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. |
|
| Change from baseline to post-treatment, over the course of 4 weeks. |
| Change from baseline to post-treatment, up to 2 months. |
| Physician Decision |
|
| BG001 | Suvorexant + EMG Only | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. Suvorexant: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG only). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. |
| BG002 | Placebo+fMRI+EMG | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Placebo: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. |
| BG003 | Suvorexant+fMRI+EMG | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. Suvorexant: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Control | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Placebo: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. |
| OG001 | Suvorexant Treatment | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. Suvorexant: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. |
|
|
|
| Primary | Startle Eyeblink Electromyographic (EMG) Response to Stress With Daily Use of Suvorexant. | Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat. | A total of 54 participants were included. Missing data was due to attrition, poor quality startle eyeblink data, or technical errors during startle data collection. | Posted | Mean | Standard Error | Standardized residual scores | Change from baseline to post-treatment, up to 2 months. |
|
|
|
|
| Primary | Percentage of Heavy Drinking Days During Daily Use of Suvorexant. | Percentage of heavy drinking days (PHDD) was calculated each week for all four weeks of the trial. A heavy drinking day was defined using NIH criteria: 5+ drinks for males and 4+ drinks for females in a single day. We conducted a multilevel mixed model with PHDD from week 1 to 4 as the within-subjects variable and treatment arm as the between subjects variable. | All 64 participants randomized to treatment were analyzed. | Posted | Mean | Standard Error | percentage of heavy drinking days | Change from baseline to post-treatment, over the course of 4 weeks. |
|
|
|
|
| Secondary | Changes in Neural Activation During Unpredictable Stress Anticipation Following Daily Use of Suvorexant. | Activation parameter estimates (arbitrary units) were extracted from anatomical bilateral aINS masks for each individual, pre and post treatment. Specifically, activation parameter estimates were extracted from anticipation of unpredictable threat > anticipation of no-threat individual contrast maps for each scanning session. Greater values reflect greater activation in the bilateral insula during the anticipation of unpredictable threat. A repeated measures analysis of variance was used to test the session (time 1 vs. time 2) by treatment arm interaction on bilateral aINS activation during unpredictable threat. Significance was set at p <.05 | A subset of participants were randomized to complete functional magnetic resonance imaging (fMRI) pre- and post-treatment. Only individuals with two scanning sessions were analyzed. | Posted | Mean | Standard Error | arbitrary units | Change from baseline to post-treatment, up to 2 months. |
|
|
|
|
| 0 |
| 18 |
| 0 |
| 18 |
| 3 |
| 18 |
| EG001 | Suvorexant + EMG Only | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. Suvorexant: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG only). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. | 0 | 18 | 0 | 18 | 3 | 18 |
| EG002 | Placebo+fMRI+EMG | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Placebo: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. | 0 | 15 | 0 | 15 | 3 | 15 |
| EG003 | Suvorexant+fMR+EMG | Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days. Suvorexant: This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. | 0 | 13 | 0 | 13 | 4 | 13 |
| Somnolence | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | Systematic Assessment |
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| Sleep Disturbances | Psychiatric disorders | Systematic Assessment |
|
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| Week 3 PHDD |
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| Week 4 PHDD |
|