Renal Cell Carcinoma
Conditions
Keywords
Renal Cell Carcinoma, Kidney Cancer
Brief summary
The primary objective of this study is to compare the effectiveness of a dose-escalation regimen (400 to 800mg bid) relative to the standard dosing regimen (400mg bid) of sorafenib given in patients with metastatic RCC. The secondary objectives are to evaluate the effects of the dose-escalation regimen on the quality of life (QoL) of patients with metastatic RCC and to characterize the safety and tolerability profile of a dose-escalation regimen of sorafenib in patients with metastatic RCC.
Interventions
DRUGSorafenib Escalated Dose
Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.
DRUGSorafenib Standard Dose
Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Sponsors
Bayer
Accelerated Community Oncology Research Network
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years old. * Diagnosis of unresectable/metastatic renal cell carcinoma (RCC). Nonclear cell histology is permitted (except for medullary, collecting duct, or sarcomatoid \>50% of specimen). Prior metastasectomy is permitted as long as there is measurable disease at time of consent. * Karnofsky Performance Status of 50% or greater at study entry. * Adequate bone marrow, liver and renal function as assessed by the following: o Hemoglobin ≥ 9.0 g/dL. o ANC ≥ 1500/mm3. o Platelet count ≥ 100,000/mm3. o Total bilirubin ≤ 1.5 ULN. o ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver involvement). o Creatinine ≤ 1.5 × ULN. * Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment. * Women of childbearing potential and sexually active men must agree to use adequate barrier contraception prior to study entry, for the duration of study participation, and for at least three months after the last administration of sorafenib. * INR \< 1.5 or a PT/ PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable. * Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
Exclusion criteria
* Prior systemic anticancer treatment for metastatic disease, including investigational therapy. * Prior treatment with bevacizumab, sunitinib, or sorafenib even in the adjuvant setting. * Prior cytokine therapy with interleukin (IL)-2 or interferon (IFN) for metastatic disease. * Active malignancy other than RCC (except non-melanoma skin cancer) within 5 years of enrollment. * Hemodialysis or peritoneal dialysis. * Treatment with radiotherapy within 2 weeks of enrollment. * Cardiac disease: Congestive heart failure Class II or higher per NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months. * Uncontrolled CNS metastases. All patients must undergo a CT) scan/MRI of the brain to exclude brain metastasis. Patients with adequately treated CNS disease may be considered for participation as long as the first dose of sorafenib is 4 weeks after completion of CNS therapy. * Uncontrolled hypertension defined as SBP \> 150 mmHg or DBP \> 90 mmHg, despite optimal medical management. * Active clinically serious infection \> Grade 2 per the CTCAE v3. * Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. * Pulmonary hemorrhage/bleeding event ≥ Grade 2 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug. * Any other hemorrhage/bleeding event ≥ Grade 3 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug. * Serious non-healing wound, ulcer, or bone fracture. * Evidence or history of bleeding diathesis or coagulopathy. * Major surgery, open biopsy or significant traumatic injury within 4 weeks of administration of the first study drug dose. * Use of St. John's Wort, rifampin (rifampicin), phenytoin, Phenobarbital, carbamazepine, dexamethasone. * Known or suspected allergy to sorafenib or any agent given in the course of this trial. * Any condition that impairs patient's ability to swallow whole pills. * Any malabsorption problem. * Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment. | Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that. Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response. Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS Rate at 9, 13 and 17 Months | PFS was to be measured at 9, 13, and 17 months. | Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated. |
| Overall Survival Rate | Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death. | Due to the early study closure and the small sample size, overall survival rate was not evaluated. |
| Changes From Baseline in Symptom Burden | The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit. | The Patient Care Monitor Version 2.0 (PCM) is an tablet computer based assessment system that measures patient reported outcomes (PROs) in medical patients with a particular emphasis on symptoms related to cancer and its treatment. The PCM comprises 86 items which include 8 items answered only by females (e.g. menstrual cramping). Each item is presented so that the patient rates the degree to which the item has been a problem in the past week (0 not a problem to 10 as bad as possible). |
Countries
United States
Participant flow
Recruitment details
13 community oncology sites across the US associated with the ACORN network participated in this study. Enrollment started in January 2008 and was closed in August 2008 due to the low rate of accrual and lack of funds beyond the current level of support from Bayer.
Pre-assignment details
Informed consent was obtained from all subjects. All subjects underwent a screening phase that could last up to 4 weeks during which pre-study assessments were completed. Eligible subjects then underwent a screening treatment phase in which they received commercial sorafenib for 4 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Screening Treatment Phase After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for \< 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4). | 12 |
| Group A: Escalated Dose Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.
Sorafenib Escalated Dose :
Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. | 4 |
| Group B: Standard Dose Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Sorafenib Standard Dose :
Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. | 2 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Screening Treatment Phase | Adverse Event | 2 | 0 | 0 |
| Screening Treatment Phase | Unable to tolerate standard dose | 3 | 0 | 0 |
| Screening Treatment Phase | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Screening Treatment Phase | Group A: Escalated Dose | Group B: Standard Dose |
|---|---|---|---|---|
| Age Continuous Randomization Phase | 63.5 years STANDARD_DEVIATION 7.18 | NA years | 66.0 years STANDARD_DEVIATION 6.38 | 58.5 years STANDARD_DEVIATION 7.78 |
| Age Continuous Screening Treatment Phase | 62.2 years STANDARD_DEVIATION 10.99 | 62.2 years STANDARD_DEVIATION 10.99 | NA years | NA years |
| Region of Enrollment United States | 0 participants | NA participants | NA participants | NA participants |
| Region of Enrollment, Customized United States (Randomization Phase) | 6 participants | NA participants | 4 participants | 2 participants |
| Region of Enrollment, Customized United States (Screening Treatment Phase) | 12 participants | 12 participants | NA participants | NA participants |
| Sex/Gender, Customized Female (Randomization Phase) | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Sex/Gender, Customized Female (Screening Treatment Phase) | 3 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex/Gender, Customized Male (Randomization Phase) | 4 Participants | 0 Participants | 2 Participants | 2 Participants |
| Sex/Gender, Customized Male (Screening Treatment Phase) | 9 Participants | 9 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 4 / 4 | 2 / 2 |
| serious Total, serious adverse events | 0 / 12 | 1 / 4 | 0 / 2 |
Outcome results
Primary
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that. Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response. Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions.
Time frame: Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: Escalated Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Complete Response (CR) | 0 Participants |
| Group A: Escalated Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Partial Response (PR) | 0 Participants |
| Group A: Escalated Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Progressive Disease (PD) | 1 Participants |
| Group A: Escalated Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Stable Disease (SD) | 3 Participants |
| Group B: Standard Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Progressive Disease (PD) | 1 Participants |
| Group B: Standard Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Partial Response (PR) | 0 Participants |
| Group B: Standard Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Stable Disease (SD) | 1 Participants |
| Group B: Standard Dose | Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Complete Response (CR) | 0 Participants |
Secondary
Changes From Baseline in Symptom Burden
The Patient Care Monitor Version 2.0 (PCM) is an tablet computer based assessment system that measures patient reported outcomes (PROs) in medical patients with a particular emphasis on symptoms related to cancer and its treatment. The PCM comprises 86 items which include 8 items answered only by females (e.g. menstrual cramping). Each item is presented so that the patient rates the degree to which the item has been a problem in the past week (0 not a problem to 10 as bad as possible).
Time frame: The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Weight Gain-Post-BL | 0.3 units on a scale | Standard Deviation 0.78 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Seeing-Baseline | 0.4 units on a scale | Standard Deviation 1.33 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Swallowing-Post-BL | 0.3 units on a scale | Standard Deviation 0.62 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Stay Out of Bed-Post-BL | 0.5 units on a scale | Standard Deviation 1.11 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Seeing-Post-BL | 1.6 units on a scale | Standard Deviation 2.9 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Change In Taste-Baseline | 0.5 units on a scale | Standard Deviation 1.27 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Itching-Baseline | 1.1 units on a scale | Standard Deviation 2.33 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Constipation-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Function Normally-Post-BL | 2.9 units on a scale | Standard Deviation 2.8 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Walk-Baseline | 0.8 units on a scale | Standard Deviation 1.72 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Constipation-Post-BL | 0.2 units on a scale | Standard Deviation 0.45 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Attend Social Activity-Post-BL | 1.8 units on a scale | Standard Deviation 2.56 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nails Change-Post-BL | 0.7 units on a scale | Standard Deviation 1.27 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Fatigue-Post-BL | 2.7 units on a scale | Standard Deviation 2.72 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Decrease in Appetite-Post-BL | 0.8 units on a scale | Standard Deviation 1.89 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Walk-Post-BL | 3.1 units on a scale | Standard Deviation 3.19 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Pain-Baseline | 0.8 units on a scale | Standard Deviation 1.14 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Diarrhea-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Mouth Sores/Ulcers-Post-BL | 0.9 units on a scale | Standard Deviation 1.53 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Day Sweat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Diarrhea-Post-BL | 0.8 units on a scale | Standard Deviation 0.88 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Crying/Feeling Like Crying-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Driving-Baseline | 0.3 units on a scale | Standard Deviation 1 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Heartburn-Baseline | 0.7 units on a scale | Standard Deviation 1.25 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hard Work or Activity-Baseline | 2.3 units on a scale | Standard Deviation 2.87 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hot Flashes/Flushes-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Heartburn-Post-BL | 1.2 units on a scale | Standard Deviation 1.67 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Crying/Feeling Like Crying-Post-BL | 0.2 units on a scale | Standard Deviation 0.46 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Constitutional Chills-Post-BL | 0.9 units on a scale | Standard Deviation 1.69 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Run-Baseline | 2 units on a scale | Standard Deviation 2.98 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Increase in Appetite-Post-BL | 0.2 units on a scale | Standard Deviation 0.48 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Pain-Post-BL | 2 units on a scale | Standard Deviation 2.51 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Weight Loss-Baseline | 0.4 units on a scale | Standard Deviation 1.26 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nausea-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Guilty-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Difficulty Hearing-Baseline | 0.7 units on a scale | Standard Deviation 2.21 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nausea-Post-BL | 0.8 units on a scale | Standard Deviation 1.11 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hard Work or Activity-Post-BL | 3.9 units on a scale | Standard Deviation 3.1 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Itching-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vomiting-Post-BL | 0.4 units on a scale | Standard Deviation 0.86 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Guilty-Post-BL | 0.2 units on a scale | Standard Deviation 0.72 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Bathe or Dress-Baseline | 0.2 units on a scale | Standard Deviation 0.67 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Menstrual Pain/Cramping-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hot Flashes/Flushes-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Problem with Urination-Baseline | 0.5 units on a scale | Standard Deviation 1.08 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Helpless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Menstrual Pain/Cramping-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Problem with Urination-Post-BL | 0.2 units on a scale | Standard Deviation 0.48 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Household Work-Baseline | 1.6 units on a scale | Standard Deviation 2.35 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Lost Interest in People-Post-BL | 0.4 units on a scale | Standard Deviation 1.03 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Bleeding-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Helpless-Post-BL | 0.4 units on a scale | Standard Deviation 0.94 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Fatigue-Baseline | 2.3 units on a scale | Standard Deviation 2.54 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Bleeding-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Hopeless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nervous, Tense, Anxious-Baseline | 1 units on a scale | Standard Deviation 1.25 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Discharge-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Weight Loss-Post-BL | 0.7 units on a scale | Standard Deviation 1.39 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Sinus Problem-Post-BL | 1.1 units on a scale | Standard Deviation 1.89 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Discharge-Post-BL | 0.1 units on a scale | Standard Deviation 0.14 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Sore Throat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hives (Welts)-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Dryness-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Hopeless-Post-BL | 0.1 units on a scale | Standard Deviation 0.43 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Dryness-Post-BL | 0 units on a scale | Standard Deviation 0.07 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Household Work-Post-BL | 2.8 units on a scale | Standard Deviation 2.29 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Bleeding-Baseline | 0.2 units on a scale | Standard Deviation 0.63 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Change In Taste-Post-BL | 0.8 units on a scale | Standard Deviation 1.41 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dry Mouth-Post-BL | 1.7 units on a scale | Standard Deviation 1.5 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Bleeding-Post-BL | 0.1 units on a scale | Standard Deviation 0.17 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling I Would Be Better Off Dead-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hives (Welts)-Post-BL | 1.2 units on a scale | Standard Deviation 2.94 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Bruising-Baseline | 0.2 units on a scale | Standard Deviation 0.63 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dry Mouth-Baseline | 0.8 units on a scale | Standard Deviation 2.04 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Night Sweat-Post-BL | 0.4 units on a scale | Standard Deviation 1.3 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Bruising-Post-BL | 0.4 units on a scale | Standard Deviation 1.35 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling I Would Be Better Off Dead-Post-BL | 0.2 units on a scale | Standard Deviation 0.47 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Bathe or Dress-Post-BL | 1.3 units on a scale | Standard Deviation 1.81 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | New Lump/Mass-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vaginal Itching-Post-BL | 0.5 units on a scale | Standard Deviation 0.51 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Sinus Problem-Baseline | 1.1 units on a scale | Standard Deviation 2.51 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | New Lump/Mass-Post-BL | 0.2 units on a scale | Standard Deviation 0.79 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Lost Interest in Pleasurable Activities-Post-BL | 0.5 units on a scale | Standard Deviation 1.3 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Worthless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Breast Tenderness-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Light Work or Activity-Baseline | 0.6 units on a scale | Standard Deviation 1.13 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Feeling Worthless-Post-BL | 0.3 units on a scale | Standard Deviation 0.69 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Breast Tenderness-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Reduced Sexual Enjoyment-Baseline | 0.2 units on a scale | Standard Deviation 0.63 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Lost Interest in People-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Attend Paid Job-Baseline | 1.1 units on a scale | Standard Deviation 2.42 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Fever-Baseline | 0.4 units on a scale | Standard Deviation 1.26 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hair Loss-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Headache-Post-BL | 0.5 units on a scale | Standard Deviation 0.6 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Chest Pain-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Hair Loss-Post-BL | 1.2 units on a scale | Standard Deviation 1.86 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Reduced Sexual Enjoyment-Post-BL | 0.4 units on a scale | Standard Deviation 1.08 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Lost Interest in Pleasurable Activities-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Day Sweat-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Itching-Post-BL | 1.7 units on a scale | Standard Deviation 2.78 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Light Work or Activity-Post-BL | 2.6 units on a scale | Standard Deviation 2.36 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Chest Pain-Post-BL | 0.3 units on a scale | Standard Deviation 0.56 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nails Change-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Cook for Self-Baseline | 0.8 units on a scale | Standard Deviation 2.33 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Thinking-Post-BL | 0 units on a scale | Standard Deviation 0.14 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Sore Throat-Post-BL | 0.4 units on a scale | Standard Deviation 0.63 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nipple Discharge-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Difficulty Hearing-Post-BL | 0.5 units on a scale | Standard Deviation 1.24 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Rapid Heart Beat-Baseline | 0.8 units on a scale | Standard Deviation 2.53 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nipple Discharge-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Nervous, Tense, Anxious-Post-BL | 0.6 units on a scale | Standard Deviation 0.87 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Run-Post-BL | 3.8 units on a scale | Standard Deviation 3.96 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Rash-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dry Eyes-Baseline | 0.7 units on a scale | Standard Deviation 2 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Sad (Depressed)-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Rash-Post-BL | 1.7 units on a scale | Standard Deviation 3 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Attend Paid Job-Post-BL | 3.8 units on a scale | Standard Deviation 3.98 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Rapid Heart Beat-Post-BL | 0.3 units on a scale | Standard Deviation 0.75 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Joint Pain-Baseline | 1 units on a scale | Standard Deviation 2.16 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Cook for Self-Post-BL | 1.6 units on a scale | Standard Deviation 2.45 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Sad (Depressed)-Post-BL | 0.5 units on a scale | Standard Deviation 0.95 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Joint Pain-Post-BL | 1.3 units on a scale | Standard Deviation 2.14 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Run Errands-Baseline | 1.7 units on a scale | Standard Deviation 3.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Night Sweat-Baseline | 1.7 units on a scale | Standard Deviation 3.65 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Muscle Aches-Baseline | 0.5 units on a scale | Standard Deviation 1.08 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Headache-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Swelling-Baseline | 0.3 units on a scale | Standard Deviation 0.95 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Muscle Aches-Post-BL | 1.2 units on a scale | Standard Deviation 2.06 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Thinking-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Worry-Baseline | 1 units on a scale | Standard Deviation 1.25 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Weakness of Body Parts-Baseline | 0.6 units on a scale | Standard Deviation 1.07 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Fever-Post-BL | 0.9 units on a scale | Standard Deviation 1.47 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dry Eyes-Post-BL | 0.9 units on a scale | Standard Deviation 1.49 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Weakness of Body Parts-Post-BL | 1.8 units on a scale | Standard Deviation 2.3 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Worry-Post-BL | 0.6 units on a scale | Standard Deviation 1.05 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Swelling-Post-BL | 1 units on a scale | Standard Deviation 2.28 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Burning Sensation in Hands or Feet-Baseline | 0.8 units on a scale | Standard Deviation 1.93 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Run Errands-Post-BL | 2.5 units on a scale | Standard Deviation 3 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Mouth Sores/Ulcers-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Burning Sensation in Hands or Feet-Post-BL | 2.3 units on a scale | Standard Deviation 3.12 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Coughing-Baseline | 1.6 units on a scale | Standard Deviation 2.95 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Swallowing-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Daytime Sleepiness-Baseline | 0.5 units on a scale | Standard Deviation 0.97 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dry Skin-Baseline | 1.4 units on a scale | Standard Deviation 2.99 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Constitutional Chills-Baseline | 0.2 units on a scale | Standard Deviation 0.63 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Daytime Sleepiness-Post-BL | 1.1 units on a scale | Standard Deviation 1.52 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Coughing-Post-BL | 1 units on a scale | Standard Deviation 2.29 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Sit Up-Baseline | 0.2 units on a scale | Standard Deviation 0.67 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dizziness/Lightheadedness-Baseline | 0.2 units on a scale | Standard Deviation 0.42 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Tearing-Baseline | 1.1 units on a scale | Standard Deviation 1.96 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Shortness of Breath-Baseline | 2.2 units on a scale | Standard Deviation 2.86 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dizziness/Lightheadedness-Post-BL | 0.4 units on a scale | Standard Deviation 0.68 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Driving-Post-BL | 1.2 units on a scale | Standard Deviation 1.68 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Decrease in Appetite-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Memory Loss-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Vomiting-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Shortness of Breath-Post-BL | 2.1 units on a scale | Standard Deviation 2.7 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Memory Loss-Post-BL | 0.3 units on a scale | Standard Deviation 0.87 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Site Up-Post-BL | 0 units on a scale | Standard Deviation 0.14 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Dry Skin-Post-BL | 2.5 units on a scale | Standard Deviation 3.34 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Numbness/Tingling-Baseline | 0 units on a scale | Standard Deviation 0 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Wheezing-Baseline | 1.2 units on a scale | Standard Deviation 2.57 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Attend Social Activity-Baseline | 0.6 units on a scale | Standard Deviation 1.67 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Numbness/Tingling-Post-BL | 0.7 units on a scale | Standard Deviation 1.35 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Tearing-Post-BL | 0.5 units on a scale | Standard Deviation 1.36 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Weight Gain-Baseline | 1.3 units on a scale | Standard Deviation 2.75 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Sleeping at Night-Baseline | 1.3 units on a scale | Standard Deviation 2.06 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Wheezing-Post-BL | 1 units on a scale | Standard Deviation 2.29 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Function Normally-Baseline | 2.3 units on a scale | Standard Deviation 3.2 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Trouble Sleeping at Night-Post-BL | 1.6 units on a scale | Standard Deviation 1.81 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Stay Out of Bed-Baseline | 0.2 units on a scale | Standard Deviation 0.67 |
| Screening Treatment Phase | Changes From Baseline in Symptom Burden | Increase in Appetite-Baseline | 0.1 units on a scale | Standard Deviation 0.32 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Muscle Aches-Post-BL | 0.8 units on a scale | Standard Deviation 0.99 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Thinking-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Thinking-Post-BL | 0.1 units on a scale | Standard Deviation 0.25 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Weight Gain-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Headache-Baseline | 0.3 units on a scale | Standard Deviation 0.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Headache-Post-BL | 0.7 units on a scale | Standard Deviation 0.55 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Weight Loss-Baseline | 1 units on a scale | Standard Deviation 2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Increase in Appetite-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Pain-Post-BL | 2.6 units on a scale | Standard Deviation 2.13 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Attend Paid Job-Baseline | 2 units on a scale | Standard Deviation 3.37 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Weight Loss-Post-BL | 1.6 units on a scale | Standard Deviation 2.14 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Attend Paid Job-Post-BL | 3.7 units on a scale | Standard Deviation 3.56 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Attend Social Activity-Baseline | 1.3 units on a scale | Standard Deviation 2.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Attend Social Activity-Post-BL | 3 units on a scale | Standard Deviation 2.68 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vomiting-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Bathe or Dress-Baseline | 0.5 units on a scale | Standard Deviation 1 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Bathe or Dress-Post-BL | 1.4 units on a scale | Standard Deviation 1.69 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dry Mouth-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Cook for Self-Baseline | 1.8 units on a scale | Standard Deviation 3.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dry Mouth-Post-BL | 2 units on a scale | Standard Deviation 1.7 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Cook for Self-Post-BL | 2.6 units on a scale | Standard Deviation 2.67 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Driving-Post-BL | 2.2 units on a scale | Standard Deviation 2.09 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Mouth Sores/Ulcers-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Function Normally-Baseline | 3.8 units on a scale | Standard Deviation 4.35 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Difficulty Hearing-Baseline | 1.8 units on a scale | Standard Deviation 3.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Function Normally-Post-BL | 3.8 units on a scale | Standard Deviation 2.88 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hard Work or Activity-Baseline | 1.3 units on a scale | Standard Deviation 1.15 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Mouth Sores/Ulcers-Post-BL | 0.6 units on a scale | Standard Deviation 1.04 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hard Work or Activity-Post-BL | 5.3 units on a scale | Standard Deviation 3.52 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Household Work-Baseline | 2.3 units on a scale | Standard Deviation 3.3 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Household Work-Post-BL | 4.2 units on a scale | Standard Deviation 2.84 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Sore Throat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Light Work or Activity-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Menstrual Pain/Cramping-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Light Work or Activity-Post-BL | 3.4 units on a scale | Standard Deviation 2.65 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Run-Baseline | 0.7 units on a scale | Standard Deviation 1.15 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Run-Post-BL | 5.9 units on a scale | Standard Deviation 3.97 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Sore Throat-Post-BL | 0.5 units on a scale | Standard Deviation 0.54 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Run Errands-Baseline | 3.8 units on a scale | Standard Deviation 4.35 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Change In Taste-Baseline | 1 units on a scale | Standard Deviation 2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Run Errands-Post-BL | 4.6 units on a scale | Standard Deviation 3.73 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Sit Up-Baseline | 0.5 units on a scale | Standard Deviation 1 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Swallowing-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Site Up-Post-BL | 0.1 units on a scale | Standard Deviation 0.25 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Dryness-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Stay Out of Bed-Baseline | 0.5 units on a scale | Standard Deviation 1 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Stay Out of Bed-Post-BL | 1.1 units on a scale | Standard Deviation 1.66 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Swallowing-Post-BL | 0.3 units on a scale | Standard Deviation 0.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Walk-Baseline | 0.5 units on a scale | Standard Deviation 1 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Walk-Post-BL | 3.4 units on a scale | Standard Deviation 2.26 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Crying/Feeling Like Crying-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Crying/Feeling Like Crying-Post-BL | 0.2 units on a scale | Standard Deviation 0.36 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hot Flashes/Flushes-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Guilty-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Guilty-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Helpless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hot Flashes/Flushes-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Hopeless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Itching-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Hopeless-Post-BL | 0.4 units on a scale | Standard Deviation 0.75 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling I Would Be Better Off Dead-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling I Would Be Better Off Dead-Post-BL | 0.2 units on a scale | Standard Deviation 0.38 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Itching-Post-BL | 0.2 units on a scale | Standard Deviation 0.27 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Lost Interest in People-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Lost Interest in People-Post-BL | 0.6 units on a scale | Standard Deviation 1.13 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Lost Interest in Pleasurable Activities-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Reduced Sexual Enjoyment-Post-BL | 0.9 units on a scale | Standard Deviation 1.75 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Lost Interest in Pleasurable Activities-Post-BL | 1.4 units on a scale | Standard Deviation 2.14 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nervous, Tense, Anxious-Baseline | 0.8 units on a scale | Standard Deviation 0.96 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nervous, Tense, Anxious-Post-BL | 0.9 units on a scale | Standard Deviation 1.15 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Sad (Depressed)-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dry Eyes-Baseline | 1.5 units on a scale | Standard Deviation 3 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Sad (Depressed)-Post-BL | 0.6 units on a scale | Standard Deviation 1.25 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Change In Taste-Post-BL | 2.2 units on a scale | Standard Deviation 1.81 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Worry-Baseline | 0.8 units on a scale | Standard Deviation 0.96 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Worry-Post-BL | 0.8 units on a scale | Standard Deviation 1.06 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dry Eyes-Post-BL | 1.4 units on a scale | Standard Deviation 1.79 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Coughing-Baseline | 2 units on a scale | Standard Deviation 4 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Coughing-Post-BL | 2.4 units on a scale | Standard Deviation 3.79 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Shortness of Breath-Baseline | 3.3 units on a scale | Standard Deviation 3.59 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Tearing-Baseline | 2.3 units on a scale | Standard Deviation 2.63 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Shortness of Breath-Post-BL | 4 units on a scale | Standard Deviation 3.47 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Wheezing-Baseline | 2 units on a scale | Standard Deviation 4 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Wheezing-Post-BL | 2 units on a scale | Standard Deviation 3.62 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Constitutional Chills-Post-BL | 0.8 units on a scale | Standard Deviation 1.32 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Tearing-Post-BL | 1.2 units on a scale | Standard Deviation 2.35 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Seeing-Baseline | 1 units on a scale | Standard Deviation 2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dry Skin-Post-BL | 3.2 units on a scale | Standard Deviation 2.72 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Seeing-Post-BL | 2 units on a scale | Standard Deviation 3.37 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Constipation-Baseline | 0.3 units on a scale | Standard Deviation 0.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Itching-Baseline | 1.3 units on a scale | Standard Deviation 2.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Constipation-Post-BL | 0.5 units on a scale | Standard Deviation 0.71 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nails Change-Post-BL | 1.9 units on a scale | Standard Deviation 1.62 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Decrease in Appetite-Post-BL | 2.4 units on a scale | Standard Deviation 2.87 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Diarrhea-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Pain-Baseline | 1.3 units on a scale | Standard Deviation 1.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Diarrhea-Post-BL | 1.1 units on a scale | Standard Deviation 0.77 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Heartburn-Baseline | 1.3 units on a scale | Standard Deviation 1.89 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Driving-Baseline | 0.8 units on a scale | Standard Deviation 1.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Heartburn-Post-BL | 2.7 units on a scale | Standard Deviation 2.17 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Increase in Appetite-Post-BL | 0.1 units on a scale | Standard Deviation 0.14 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Helpless-Post-BL | 0.8 units on a scale | Standard Deviation 1.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nausea-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nausea-Post-BL | 1.4 units on a scale | Standard Deviation 1.53 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Difficulty Hearing-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vomiting-Post-BL | 1.1 units on a scale | Standard Deviation 1.31 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Worthless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Menstrual Pain/Cramping-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Problem with Urination-Baseline | 1.3 units on a scale | Standard Deviation 1.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Feeling Worthless-Post-BL | 0.6 units on a scale | Standard Deviation 1.13 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Problem with Urination-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Bleeding-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Bleeding-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Discharge-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Discharge-Post-BL | 0.1 units on a scale | Standard Deviation 0.18 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hives (Welts)-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Vaginal Dryness-Post-BL | 0.1 units on a scale | Standard Deviation 0.09 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Bleeding-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Bleeding-Post-BL | 0.1 units on a scale | Standard Deviation 0.25 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Bruising-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hives (Welts)-Post-BL | 0.2 units on a scale | Standard Deviation 0.38 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Bruising-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Reduced Sexual Enjoyment-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | New Lump/Mass-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | New Lump/Mass-Post-BL | 0.7 units on a scale | Standard Deviation 1.38 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Sinus Problem-Baseline | 2.3 units on a scale | Standard Deviation 3.86 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Breast Tenderness-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Day Sweat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Breast Tenderness-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dry Skin-Baseline | 2 units on a scale | Standard Deviation 4 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Sinus Problem-Post-BL | 2.4 units on a scale | Standard Deviation 2.54 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hair Loss-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Hair Loss-Post-BL | 3.3 units on a scale | Standard Deviation 1.9 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Chest Pain-Baseline | 0.3 units on a scale | Standard Deviation 0.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Itching-Post-BL | 1.2 units on a scale | Standard Deviation 0.85 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nails Change-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Chest Pain-Post-BL | 0.4 units on a scale | Standard Deviation 0.54 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Day Sweat-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nipple Discharge-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Nipple Discharge-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Rapid Heart Beat-Baseline | 2 units on a scale | Standard Deviation 4 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Rash-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Fever-Baseline | 1 units on a scale | Standard Deviation 2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Rash-Post-BL | 1.1 units on a scale | Standard Deviation 2.09 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Joint Pain-Baseline | 1 units on a scale | Standard Deviation 2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Rapid Heart Beat-Post-BL | 0.9 units on a scale | Standard Deviation 1.2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Joint Pain-Post-BL | 0.9 units on a scale | Standard Deviation 1.06 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Muscle Aches-Baseline | 0.5 units on a scale | Standard Deviation 1 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Swelling-Baseline | 0.8 units on a scale | Standard Deviation 1.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Weakness of Body Parts-Baseline | 1 units on a scale | Standard Deviation 1.41 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Night Sweat-Baseline | 4.3 units on a scale | Standard Deviation 5.06 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Weakness of Body Parts-Post-BL | 4 units on a scale | Standard Deviation 2.74 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Burning Sensation in Hands or Feet-Baseline | 2 units on a scale | Standard Deviation 2.83 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Swelling-Post-BL | 0 units on a scale | Standard Deviation 0.06 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Burning Sensation in Hands or Feet-Post-BL | 2.6 units on a scale | Standard Deviation 2.62 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Night Sweat-Post-BL | 1.1 units on a scale | Standard Deviation 2.25 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Daytime Sleepiness-Baseline | 0.8 units on a scale | Standard Deviation 1.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Daytime Sleepiness-Post-BL | 1.9 units on a scale | Standard Deviation 1.91 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Constitutional Chills-Baseline | 0.5 units on a scale | Standard Deviation 1 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dizziness/Lightheadedness-Baseline | 0.5 units on a scale | Standard Deviation 0.58 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Fatigue-Baseline | 3.8 units on a scale | Standard Deviation 3.3 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Dizziness/Lightheadedness-Post-BL | 0.8 units on a scale | Standard Deviation 0.78 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Memory Loss-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Fatigue-Post-BL | 5 units on a scale | Standard Deviation 3.22 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Memory Loss-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Fever-Post-BL | 1.4 units on a scale | Standard Deviation 2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Numbness/Tingling-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Decrease in Appetite-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Numbness/Tingling-Post-BL | 0.2 units on a scale | Standard Deviation 0.19 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Sleeping at Night-Baseline | 1 units on a scale | Standard Deviation 2 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Weight Gain-Baseline | 1.8 units on a scale | Standard Deviation 3.5 |
| Group A: Escalated Dose | Changes From Baseline in Symptom Burden | Trouble Sleeping at Night-Post-BL | 2.5 units on a scale | Standard Deviation 2.28 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Wheezing-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Constitutional Chills-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Difficulty Hearing-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Fatigue-Post-BL | 0.5 units on a scale | Standard Deviation 0.71 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Fever-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Weight Gain-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Change In Taste-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Change In Taste-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dry Mouth-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Day Sweat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Day Sweat-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Reduced Sexual Enjoyment-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vomiting-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vomiting-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Menstrual Pain/Cramping-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Dryness-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Itching-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Itching-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Breast Tenderness-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Light Work or Activity-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Helpless-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Lost Interest in People-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Lost Interest in Pleasurable Activities-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hives (Welts)-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hives (Welts)-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Sinus Problem-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Sinus Problem-Post-BL | 0.1 units on a scale | Standard Deviation 0.11 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Chest Pain-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Chest Pain-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Rapid Heart Beat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Rapid Heart Beat-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Swelling-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Swelling-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Constitutional Chills-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Fatigue-Baseline | 2 units on a scale | Standard Deviation 2.83 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Fever-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Weight Gain-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Weight Loss-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Weight Loss-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Difficulty Hearing-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dry Mouth-Post-BL | 2.7 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Mouth Sores/Ulcers-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Mouth Sores/Ulcers-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Sore Throat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Sore Throat-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Swallowing-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Swallowing-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hot Flashes/Flushes-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hot Flashes/Flushes-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Night Sweat-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Tearing-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Night Sweat-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Reduced Sexual Enjoyment-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dry Eyes-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dry Eyes-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Tearing-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Seeing-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Seeing-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Constipation-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Constipation-Post-BL | 0.3 units on a scale | Standard Deviation 0.35 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Decrease in Appetite-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Decrease in Appetite-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Diarrhea-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Diarrhea-Post-BL | 1.3 units on a scale | Standard Deviation 1.88 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Heartburn-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Heartburn-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Increase in Appetite-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Increase in Appetite-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nausea-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nausea-Post-BL | 0.5 units on a scale | Standard Deviation 0.71 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Menstrual Pain/Cramping-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Problem with Urination-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Problem with Urination-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Bleeding-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Bleeding-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Discharge-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Discharge-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Vaginal Dryness-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Bleeding-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Bleeding-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Bruising-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Bruising-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | New Lump/Mass-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | New Lump/Mass-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Breast Tenderness-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dry Skin-Baseline | 3 units on a scale | Standard Deviation 4.24 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dry Skin-Post-BL | 0.2 units on a scale | Standard Deviation 0.33 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hair Loss-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hair Loss-Post-BL | 0.5 units on a scale | Standard Deviation 0.65 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Itching-Baseline | 3 units on a scale | Standard Deviation 4.24 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Itching-Post-BL | 0.1 units on a scale | Standard Deviation 0.19 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nails Change-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nails Change-Post-BL | 0.1 units on a scale | Standard Deviation 1.6 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nipple Discharge-Baseline | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nipple Discharge-Post-BL | NA units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Rash-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Rash-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Joint Pain-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Joint Pain-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Muscle Aches-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Muscle Aches-Post-BL | 0.3 units on a scale | Standard Deviation 0.35 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Weakness of Body Parts-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Weakness of Body Parts-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Burning Sensation in Hands or Feet-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Burning Sensation in Hands or Feet-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Daytime Sleepiness-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Daytime Sleepiness-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dizziness/Lightheadedness-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Dizziness/Lightheadedness-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Memory Loss-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Memory Loss-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Numbness/Tingling-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Numbness/Tingling-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Sleeping at Night-Baseline | 3 units on a scale | Standard Deviation 4.24 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Sleeping at Night-Post-BL | 1 units on a scale | Standard Deviation 1.41 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Thinking-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Trouble Thinking-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Headache-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Headache-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Pain-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Pain-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Attend Paid Job-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Attend Paid Job-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Attend Social Activity-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Attend Social Activity-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Bathe or Dress-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Bathe or Dress-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Cook for Self-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Cook for Self-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Driving-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Driving-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Function Normally-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Function Normally-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hard Work or Activity-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Hard Work or Activity-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Household Work-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Household Work-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Light Work or Activity-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Run-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Run-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Run Errands-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Run Errands-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Sit Up-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Site Up-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Stay Out of Bed-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Stay Out of Bed-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Walk-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Walk-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Crying/Feeling Like Crying-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Crying/Feeling Like Crying-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Guilty-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Guilty-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Helpless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Hopeless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Hopeless-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling I Would Be Better Off Dead-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling I Would Be Better Off Dead-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Worthless-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Feeling Worthless-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Lost Interest in People-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Lost Interest in Pleasurable Activities-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nervous, Tense, Anxious-Baseline | 1.5 units on a scale | Standard Deviation 2.12 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Nervous, Tense, Anxious-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Sad (Depressed)-Baseline | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Sad (Depressed)-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Worry-Baseline | 1.5 units on a scale | Standard Deviation 2.12 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Worry-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Coughing-Baseline | 3 units on a scale | Standard Deviation 4.24 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Coughing-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Shortness of Breath-Baseline | 0 units on a scale | — |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Shortness of Breath-Post-BL | 0 units on a scale | Standard Deviation 0 |
| Group B: Standard Dose | Changes From Baseline in Symptom Burden | Wheezing-Baseline | 0.5 units on a scale | Standard Deviation 0.71 |
Secondary
Overall Survival Rate
Due to the early study closure and the small sample size, overall survival rate was not evaluated.
Time frame: Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.
Population: Due to the early study closure and the small sample size, overall survival rate was not evaluated.
Secondary
PFS Rate at 9, 13 and 17 Months
Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.
Time frame: PFS was to be measured at 9, 13, and 17 months.
Population: Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.
Post Hoc
Median Progression Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. Progression is defined per RECIST criteria as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions. The median progression free survival is the parameter used to describe PFS.
Time frame: PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever occurred first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Screening Treatment Phase | Median Progression Free Survival (PFS) | 11.37 Months |
| Group A: Escalated Dose | Median Progression Free Survival (PFS) | 5.77 Months |
| Group B: Standard Dose | Median Progression Free Survival (PFS) | NA Months |