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This is a multicenter Phase 2, multiple dose, dose escalation study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SPR001 in adult patients with classic congenital adrenal hyperplasia (CAH).
This is a 6-week, multiple-dose, dose escalation study of SPR001 for the treatment of adults with classic CAH. After screening, eligible patients will be enrolled into a 6-week treatment period followed by a 4-week washout/safety follow-up period.
It is initially planned that up to approximately 18 patients in 2 dose cohorts will be enrolled. Additional patients or dose groups may be considered based upon specific safety, PK/PD, and/or efficacy findings, or if an active dose has not yet been reached.
SPR001 will be administered as an oral daily dose. Patients will undergo titration of SPR001 through three escalating dosage strengths at 2-week intervals. Patients will have overnight PK/PD assessments performed at baseline, which include an pre-dose overnight assessment and a post-dose overnight assessment for PK/PD following administration of the first dose. At the end of each 2-week dosing period, patients will return for single overnight visits for steady-state PK/PD assessments.
A follow-up outpatient visit will occur 30 days after their last dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A | Experimental | The first cohort of 9 patients will be administered SPR001 at dose strength of Dose A daily for 2 weeks, and escalating through Dose B per day for 2 weeks and Dose C per day for 2 weeks. |
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| Cohort B | Experimental | Cohort B will begin enrollment after Cohort A has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort B will be determined by an interim review of safety and PK/PD data from from Cohort A. |
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| Cohort C | Experimental | Cohort C will begin enrollment after Cohort B has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort C will be determined by an interim review of safety and PK/PD data from from Cohort A and B. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SPR001 | Drug | SPR001 Capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety of SPR001 in Patients With CAH | Incidence of treatment-emergent adverse events, changes from Baseline to End-of-study in clinical laboratory parameters, physical examination findings, vital signs, ECG parameters | 6 weeks |
| Change in 17-hydroxyprogesterone | Change in 17-hydroxyprogesterone from Baseline to End-of-study. Results are expressed as mean percent change from baseline. Reductions in 17-OHP are indicators of better disease control. | Cohort A: Baseline/2a (Day -1-0), First dose/2b (Day 0-1), Visit 3 (Day 13-14), Visit 4 (Day 27-28), Visit 5 (Day 41-42). Cohort B and Cohort C: Visit 2 (Day 0-1), Visit 3 (Day 8), Visit 4 (Day 14-15), Visit 5 (Last dose +30d) |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Pharmacodynamic (PD) Markers | Changes in adrenocorticotropic hormone (ACTH) and androstenedione (A4) from Baseline to End-of-study are measured in patient serum. Results are expressed as a mean percentage change from baseline. A negative change indicates improvement. | Cohort A: Visit 2a (Day -1 to 0), Visit 2b (Days 0-1), Visit 3 (Day 13-14), Visit 4 (Day 27-28), Visit 5 (Day 41 to 42). Cohorts B+C: Visit 2 (Day 0-1), Visit 3 (Day 8), Visit 4 (Day 27-28), Visit 5 (+30 days after last dose) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Spruce Chief Medical Officer, MD | Spruce Biosciences | Study Director |
| Richard Auchus, MD, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spruce Biosciences Clinical Site | Orange | California | 92123 | United States | ||
| Spruce Biosciences Clinical Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34146101 | Result | Sarafoglou K, Barnes CN, Huang M, Imel EA, Madu IJ, Merke DP, Moriarty D, Nakhle S, Newfield RS, Vogiatzi MG, Auchus RJ. Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4666-e4679. doi: 10.1210/clinem/dgab438. |
| Label | URL |
|---|---|
| On-line clinical study-related information for patients, including pre-screening questionnaire. | View source |
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A total of 24 subjects were enrolled into the study and 24 ICFs were signed. Two subjects were enrolled in more than one cohort: one subject was enrolled in both Cohorts A and C and one subject was enrolled in both in Cohorts A and B. Therefore, the total when adding Cohorts A+B+C = 26; however, 2 subject were the same, thus a total of 24 unique subjects participated and signed the ICFs.
No participants enrolled in Period 4: Cohort D
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| ID | Title | Description |
|---|---|---|
| FG000 | Period 1: Cohort A | The first cohort of 9 patients underwent dose escalation through 3 dose levels of tildacerfont capsules, beginning with 200 mg QD for 2 weeks, then escalating to 600 mg QD/day for 2 weeks, then escalating to 1000 mg QD for 2 weeks with no washout between dose levels. |
| FG001 | Period 2: Cohort B | Cohort B will begin enrollment after Cohort A has been fully enrolled. Cohorts B, C, and D underwent a 2-week run-in period, a 2-week treatment period, and a 30-day washout and safety follow-up period. Cohort B was administered tildacerfont 200 mg BID during the treatment period. |
| FG002 | Period 3: Cohort C | Cohort C will begin enrollment after Cohort B has been fully enrolled. Cohorts B, C, and D underwent a 2-week run-in period, a 2-week treatment period, and a 30-day washout and safety follow-up period. Cohort C was administered tildacerfont 100 mg BID during the treatment period. |
| FG003 | Period 4: Cohort D | Cohort D will begin enrollment after Cohort C has been fully enrolled. Cohorts B, C, and D underwent a 2-week run-in period, a 2-week treatment period, and a 30-day washout and safety follow-up period. For Cohort D, the dose level and the frequency and timing of dosing were to be determined based on interim data from the previous cohorts, but the dose level of Cohort D was to be capped at 800 mg/day. Based on PK/PD results from Cohorts B and C, this cohort was not enrolled. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cohort A |
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| Cohort B |
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| Cohort C |
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24 unique subjects participated in the study; however, two subjects were enrolled in more than one cohort, one subject in Cohorts A and C and one subject in Cohorts A and B. For the subjects enrolled in more than 1 cohort, cohort totals/statistics reflect all baseline values.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A | The first cohort of 9 patients underwent dose escalation through 3 dose levels of tildacerfont capsules, beginning with 200 mg QD for 2 weeks, then escalating to 600 mg QD/day for 2 weeks, then escalating to 1000 mg QD for 2 weeks with no washout between dose levels. |
| BG001 | Cohort B |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Cohort A is reported separately from Cohorts B and C |
| 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 | Safety of SPR001 in Patients With CAH | Incidence of treatment-emergent adverse events, changes from Baseline to End-of-study in clinical laboratory parameters, physical examination findings, vital signs, ECG parameters | This full analysis set includes all subjects who received at least 1 dose of study drug. The FAS was used to analyze all safety data | Posted | Count of Participants | Participants | 6 weeks |
|
6-week treatment period followed by a 4-week washout/safety follow-up period
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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 | Cohort A - Dose A | The first cohort of 9 patients will be administered SPR001 at dose strength of Dose A daily for 2 weeks and escalating through Dose B per day for 2 weeks and Dose C per day for 2 weeks. SPR001: SPR001 Capsules |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry mouth | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Spruce Clinical Trials | Spruce Biosciences, Inc. | 415-655-4169 | clinicaltrials@sprucebio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 23, 2018 | Feb 26, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 3, 2019 | Feb 26, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000312 | Adrenal Hyperplasia, Congenital |
| ID | Term |
|---|---|
| D047808 | Adrenogenital Syndrome |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D052776 | Female Urogenital Diseases |
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| Pharmacokinetic Parameter - Maximum Plasma Concentration (Cmax) | To evaluate the pharmacokinetic (PK) parameter of maximum plasma concentration (Cmax) of SPR001 in patients with CAH. | Serial PK sampling was performed at the end of the 2 weeks for all cohorts and dose levels |
| Pharmacokinetic Parameter - Area Under the Concentration-time Curve (AUC) | To evaluate the PK parameter of area under the concentration-time curve (AUC) of SPR001 in patients with CAH | For Cohort A, serial blood collections were made for PK measurements on Day 1 for 200 mg SD and at Week 2 for all QD dose levels. In Cohorts B and C, serial blood samples were drawn for PK measurements at the end of the 2-week treatment period. |
| San Diego |
| California |
| 92123 |
| United States |
| Spruce Biosciences Clinical Site | Melbourne | Florida | 32935 | United States |
| Spruce Biosciences Clinical Site | Atlanta | Georgia | 30046 | United States |
| Spruce Biosciences Clinical Site | Indianapolis | Indiana | 46202 | United States |
| Spruce Biosciences Clinical Site | Ann Arbor | Michigan | 48109 | United States |
| Spruce Biosciences Clinical Site | Minneapolis | Minnesota | 55414 | United States |
| Spruce Biosciences Clinical Site | Las Vegas | Nevada | 89148 | United States |
| Spruce Biosciences Clinical Site | Philadelphia | Pennsylvania | 19104 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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Cohort B will begin enrollment after Cohort A has been fully enrolled. Cohorts B, C, and D underwent a 2-week run-in period, a 2-week treatment period, and a 30-day washout and safety follow-up period. Cohort B was administered tildacerfont 200 mg BID during the treatment period. |
| BG002 | Cohort C | Cohort C will begin enrollment after Cohort B has been fully enrolled. Cohorts B, C, and D underwent a 2-week run-in period, a 2-week treatment period, and a 30-day washout and safety follow-up period. Cohort C was administered tildacerfont 100 mg BID during the treatment period. |
| BG003 | Cohort D | Cohort D will begin enrollment after Cohort C has been fully enrolled. Cohorts B, C, and D underwent a 2-week run-in period, a 2-week treatment period, and a 30-day washout and safety follow-up period. For Cohort D, the dose level and the frequency and timing of dosing were to be determined based on interim data from the previous cohorts, but the dose level of Cohort D was to be capped at 800 mg/day. Based on PK/PD results from Cohorts B and C, this cohort was not enrolled. |
| BG004 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
| No |
|
| Sex: Female, Male | Cohort A is reported separately from Cohorts B and C | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Cohort A is reported separately from Cohorts B and C | Count of Participants | Participants | No |
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| Race (NIH/OMB) | Cohort A is reported separately from Cohorts B and C | Count of Participants | Participants | No |
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| Region of Enrollment | Number | participants |
|
| Body Mass Index (kg/m^2) | Body mass index (BMI) is a medical screening tool that measures the ratio of a subject's height to their weight to estimate the amount of body fat. BMI is calculated by using weight in kilograms (kg) divided by the square of height in meters (m2). | Mean | Standard Deviation | kg/m^2 |
|
Cohort B will begin enrollment after Cohort A has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort B will be determined by an interim review of safety and PK/PD data from from Cohort A.
SPR001: SPR001 Capsules
| OG002 | Cohort C | Cohort C will begin enrollment after Cohort B has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort C will be determined by an interim review of safety and PK/PD data from from Cohort A and B. SPR001: SPR001 Capsules |
|
|
| Primary | Change in 17-hydroxyprogesterone | Change in 17-hydroxyprogesterone from Baseline to End-of-study. Results are expressed as mean percent change from baseline. Reductions in 17-OHP are indicators of better disease control. | Only subjects with both baseline and post baseline (week 2) assessments were summarized. Baseline values were collected at 8am on Visit 2a (Day -1) and post-baseline Week 2 values were collected at 8a on Visit 3, Visit 4, or Visit 5. A negative change indicates improvement. | Posted | Mean | Standard Deviation | percentage of mean change from baseline | Cohort A: Baseline/2a (Day -1-0), First dose/2b (Day 0-1), Visit 3 (Day 13-14), Visit 4 (Day 27-28), Visit 5 (Day 41-42). Cohort B and Cohort C: Visit 2 (Day 0-1), Visit 3 (Day 8), Visit 4 (Day 14-15), Visit 5 (Last dose +30d) |
|
|
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| Secondary | Changes in Pharmacodynamic (PD) Markers | Changes in adrenocorticotropic hormone (ACTH) and androstenedione (A4) from Baseline to End-of-study are measured in patient serum. Results are expressed as a mean percentage change from baseline. A negative change indicates improvement. | Only subjects with both baseline and post baseline (week 2) assessments were summarized. Baseline values were collected at 8am on Visit 2a (Day -1) and post-baseline Week 2 values were collected at 8a on Visit 3, Visit 4, or Visit 5. | Posted | Mean | Standard Error | percentage of mean change from baseline | Cohort A: Visit 2a (Day -1 to 0), Visit 2b (Days 0-1), Visit 3 (Day 13-14), Visit 4 (Day 27-28), Visit 5 (Day 41 to 42). Cohorts B+C: Visit 2 (Day 0-1), Visit 3 (Day 8), Visit 4 (Day 27-28), Visit 5 (+30 days after last dose) |
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| Secondary | Pharmacokinetic Parameter - Maximum Plasma Concentration (Cmax) | To evaluate the pharmacokinetic (PK) parameter of maximum plasma concentration (Cmax) of SPR001 in patients with CAH. | Posted | Mean | Standard Deviation | ng/dL | Serial PK sampling was performed at the end of the 2 weeks for all cohorts and dose levels |
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| Secondary | Pharmacokinetic Parameter - Area Under the Concentration-time Curve (AUC) | To evaluate the PK parameter of area under the concentration-time curve (AUC) of SPR001 in patients with CAH | Posted | Mean | Standard Deviation | ng*hr/dL | For Cohort A, serial blood collections were made for PK measurements on Day 1 for 200 mg SD and at Week 2 for all QD dose levels. In Cohorts B and C, serial blood samples were drawn for PK measurements at the end of the 2-week treatment period. |
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| 0 |
| 10 |
| 0 |
| 10 |
| 6 |
| 10 |
| EG001 | Cohort A - Dose B | The first cohort of 9 patients will be administered SPR001 at dose strength of Dose A daily for 2 weeks and escalating through Dose B per day for 2 weeks and Dose C per day for 2 weeks. | 0 | 10 | 0 | 10 | 3 | 10 |
| EG002 | Cohort A - Dose C | The first cohort of 9 patients will be administered SPR001 at dose strength of Dose A daily for 2 weeks and escalating through Dose B per day for 2 weeks and Dose C per day for 2 weeks. | 0 | 9 | 0 | 10 | 3 | 9 |
| EG003 | Cohort B | Cohort B will begin enrollment after Cohort A has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort B will be determined by an interim review of safety and PK/PD data from from Cohort A. One subject from Cohort A was allowed to enroll in Cohort B. SPR001: SPR001 Capsules | 0 | 9 | 0 | 9 | 5 | 9 |
| EG004 | Cohort C | Cohort C will begin enrollment after Cohort B has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort C will be determined by an interim review of safety and PK/PD data from from Cohort B. One subject from Cohort A was allowed to enroll in Cohort C. SPR001: SPR001 Capsules | 0 | 7 | 0 | 7 | 4 | 7 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hunger | General disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Disorientation | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Ear discomfort | Ear and labyrinth disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Salivary gland enlargement | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Chills | General disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Feeling hot | General disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
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| Blood thyroid stimulating hormone increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
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| Increased appetite | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Muscle spasm | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
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| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D043202 | Steroid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Androstenedione (A4) |
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