Vasomotor Symptoms (VMS)
Conditions
Keywords
Vasomotor Symptoms, Breast Cancer, Hot Flashes, Tamoxifen, Aromatase Inhibitors, Estrogen Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, Hormone Antagonists, Physiological Effects of Drugs, Antineoplastic Agents, Hormonal Antineoplastic, Selective Estrogen Receptor Modulators, Estrogen Receptor Modulators, Bone Density Conservation Agents, Steroid Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
Brief summary
Open-label, two dose study of Q-122, over a 4 week treatment period to explore the effects of Q-122 in a population of women with a history of breast cancer taking an aromatase inhibitor or tamoxifen.
Detailed description
Vasomotor symptoms are significant in postmenopausal women with the most effective medications for relief being hormonal preparations. Non-hormonal medications have demonstrated efficacy but at a far lower level than estrogen replacement therapy. For women with a history of breast cancer hormone replacement therapy is problematic especially if their therapeutic regime involves an aromatase inhibitor. Therefore, this study will explore the effect of Q-122 in a population of women with a history of breast cancer taking an aromatase inhibitor or tamoxifen. The study is an open-label, two dose study (Group 1: 100 mg once daily and Group 2: 200 mg once daily) of Q-122, over a 4 week treatment period. As eligible subjects are enrolled, they will be assigned to Group 1 until Group 1 is fully enrolled. Dose escalation to the 200 mg level will only occur following a review of the safety experience of at least 6 subjects treated with 100 mg Q-122 once daily for at least 2 weeks. Once Group 1 is fully enrolled, eligible subjects will be enrolled into Group 2. A two-week screening phase will be used to establish a stable baseline of vasomotor symptoms and to establish study eligibility. Qualified subjects will be treated with Q-122 for four weeks either at 100 mg/day dose or the 200 mg/day dose, during which time they will be evaluated for safety, tolerability, and pharmacokinetics of Q-122 and tamoxifen levels; subjects will continue to record their hot flashes in identical fashion to the screening period. Following the 28 day treatment, period subjects who complete the study will continue to record their hot flashes for a two week follow up period.
Interventions
DRUGoral capsule of Q-122
Sponsors
Que Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label, two dose study
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Be a female of any race between the ages of 30-70 years. * History of breast cancer and presently taking an aromatase inhibitor or tamoxifen. * Naturally menopausal: ≥ 12 months spontaneous amenorrhea or \> 6 but \< 12 months amenorrhea with a serum follicle stimulating hormone (FSH) level of \> 40 mIU/mL (Milli-international Units Per Milliliter). * Surgically menopausal with an FSH level \> 40 mIU/mL. * Have a minimum of 7 moderate to severe hot flushes/day or 50 moderate to severe hot flushes per week, as verified for both weeks during the 14-day Screening Phase, prior to enrollment into the treatment phase of the study. * Able to read, understand and complete the required subject diary. * Willing and able to complete the daily subject diary, attend all study visits, and participate in all study procedures, including PK blood draws.
Exclusion criteria
* Childbearing potential, including pregnancy, or lactation. * Undiagnosed abnormal genital bleeding. * Significant day-to-day variability in hot flushes. * Participation in another clinical trial within 30 days prior to screening or during the study. * Legal incapacity or limited legal capacity. * Chronic renal (serum creatinine \> 2.0 mg/dL) or hepatic disease \[SGPT (ALT) or SGOT (AST) \> 2X normal limits\]. * Gastrointestinal, liver, kidney or other conditions which could interfere with the absorption, distribution, metabolism or excretion of Q-122. * Untreated overt hyperthyroidism. * Use of thyroid medication of less than 12 weeks on a stable dose. * Any clinically important systemic disease in the judgement of the investigator. * Inability to complete all study visits and study assessments for scheduling or other reasons. * Any other reason which in the investigator's opinion makes the subject unsuitable for a clinical trial. * Abnormal laboratory findings including: 1. Hematocrit \< 30% or hemoglobin \< 9.5 gm/dL 2. Fasting blood sugar \> 140 mg/dL 3. Fasting serum triglycerides \> 300 mg/dL 4. Fasting SGOT, SGPT, GGT, or bilirubin greater than twice the upper limit of normal (a subject will not be excluded if a second measurement is less than twice the upper limit of normal) 5. Creatinine \> 2.0 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event (AE) Reporting of Q-122 | 4 weeks | Number of participants with indicated AE receiving Q-122 |
| Serious Adverse Event (SAE) Reporting of Q-122 | 4 weeks | Number of participants with indicated SAE receiving Q-122 |
| Change in Frequency of Moderate to Severe Vasomotor Symptoms. | Baseline to 4 weeks | Mean change in frequency of moderate to severe vasomotor symptoms. Daily patient (paper) diaries will be used as the primary efficacy collection tool. Change from baseline represents the mean change from the daily average frequency calculated at baseline to the daily average frequency calculated for the last week the subject was on drug. The hot flash severity categories are defined clinically as follow: mild, sensation of heat without perspiration; moderate, sensation of heat with perspiration, but subject is able to continue with activity; and severe. sensation of heat with sweating, sufficiently severe to result in discontinuation of activity. |
| Percent Change in Frequency of Moderate to Severe Vasomotor Symptoms. | Baseline to 4 weeks | Percent reduction in frequency of moderate to severe vasomotor symptoms. Daily patient (paper) diaries will be used as the primary efficacy collection tool. The hot flash severity categories are defined clinically as follows: mild, sensation of heat without perspiration; moderate, sensation of heat with perspiration, but subject is able to continue with activity; and severe, sensation of heat with sweating, sufficiently severe to result in discontinuation of activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Hot Flash Severity Score | Baseline to 4 weeks | For moderate-to-severe (mod/sev) hot flashes (HF), a score will be calculated by multiplying the number of moderate-to-severe HFs by their severity to determine the HF (mod/sev) index score, using the following formula: HFSSmod/sev = (number of moderate hot flashes/day × 2) + (number of severe hot flashes/day x 3). The Average Daily HFSSmod/sev for each week will be calculated by dividing the total of daily HFSSmod/sev by the number of days observations will be recorded in that week. |
| Symptoms Associated With Postmenopausal Status | Baseline and 4 weeks | Greene Climacteric Scale: A comprehensive assessment divided into psychological, physical and vasomotor areas. The scale includes 21 symptoms, subject will score the severity of each symptom with the following score system: 0 = not at all; 1 = a little; 2 = quite a bit; and 3 = extremely. The results represent the total combined score, which can range from 0 to 63. A lower score represents a better outcome. |
| Change in Hot Flash Severity Score | Baseline to 4 weeks | For moderate-to-severe (mod/sev) hot flashes (HF), a score will be calculated by multiplying the number of moderate-to-severe HFs by their severity to determine the HF (mod/sev) index score, using the following formula: HFSSmod/sev = (number of moderate hot flashes/day × 2) + (number of severe hot flashes/day x 3). The Average Daily HFSSmod/sev for each week will be calculated by dividing the total of daily HFSSmod/sev by the number of days observations will be recorded in that week. The change in score is of clinical significance, with a lower score representing less moderate to severe hot flashes and a higher score representing a greater number of moderate to severe hot flashes. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 100 mg Q-122 Dosage was 100 mg Q-122 administered orally as two 50 mg capsules once daily for 28 days. | 10 |
| 200 mg Q-122 Dosage was 200 mg Q-122 administered orally as four 50 mg capsules once daily for 28 days. | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | concurrent illness | 1 | 0 |
Baseline characteristics
| Characteristic | 200 mg Q-122 | Total | 100 mg Q-122 |
|---|---|---|---|
| Age, Continuous | 57 years | 56.8 years | 56.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 19 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 7 / 10 | 7 / 11 |
| serious Total, serious adverse events | 0 / 10 | 1 / 11 |
Outcome results
Primary
Adverse Event (AE) Reporting of Q-122
Number of participants with indicated AE receiving Q-122
Time frame: 4 weeks
Population: Analyses were performed using the results from the safety analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg Q-122 | Adverse Event (AE) Reporting of Q-122 | 7 Participants |
| 200 mg Q-122 | Adverse Event (AE) Reporting of Q-122 | 7 Participants |
Primary
Change in Frequency of Moderate to Severe Vasomotor Symptoms.
Mean change in frequency of moderate to severe vasomotor symptoms. Daily patient (paper) diaries will be used as the primary efficacy collection tool. Change from baseline represents the mean change from the daily average frequency calculated at baseline to the daily average frequency calculated for the last week the subject was on drug. The hot flash severity categories are defined clinically as follow: mild, sensation of heat without perspiration; moderate, sensation of heat with perspiration, but subject is able to continue with activity; and severe. sensation of heat with sweating, sufficiently severe to result in discontinuation of activity.
Time frame: Baseline to 4 weeks
Population: Analyses were performed using the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg Q-122 | Change in Frequency of Moderate to Severe Vasomotor Symptoms. | Baseline | 9.86 Hot flashes/day | Standard Deviation 3.18 |
| 100 mg Q-122 | Change in Frequency of Moderate to Severe Vasomotor Symptoms. | Change from baseline | -5.81 Hot flashes/day | Standard Deviation 3.71 |
| 200 mg Q-122 | Change in Frequency of Moderate to Severe Vasomotor Symptoms. | Baseline | 8.58 Hot flashes/day | Standard Deviation 1.63 |
| 200 mg Q-122 | Change in Frequency of Moderate to Severe Vasomotor Symptoms. | Change from baseline | -5.60 Hot flashes/day | Standard Deviation 3.13 |
Primary
Percent Change in Frequency of Moderate to Severe Vasomotor Symptoms.
Percent reduction in frequency of moderate to severe vasomotor symptoms. Daily patient (paper) diaries will be used as the primary efficacy collection tool. The hot flash severity categories are defined clinically as follows: mild, sensation of heat without perspiration; moderate, sensation of heat with perspiration, but subject is able to continue with activity; and severe, sensation of heat with sweating, sufficiently severe to result in discontinuation of activity.
Time frame: Baseline to 4 weeks
Population: Analyses were performed using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 mg Q-122 | Percent Change in Frequency of Moderate to Severe Vasomotor Symptoms. | -61.46 Percent change | Standard Deviation 38.85 |
| 200 mg Q-122 | Percent Change in Frequency of Moderate to Severe Vasomotor Symptoms. | -67.55 Percent change | Standard Deviation 39.27 |
Primary
Serious Adverse Event (SAE) Reporting of Q-122
Number of participants with indicated SAE receiving Q-122
Time frame: 4 weeks
Population: Analyses were performed using the results from the safety analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg Q-122 | Serious Adverse Event (SAE) Reporting of Q-122 | 0 Participants |
| 200 mg Q-122 | Serious Adverse Event (SAE) Reporting of Q-122 | 1 Participants |
Secondary
Change in Hot Flash Severity Score
For moderate-to-severe (mod/sev) hot flashes (HF), a score will be calculated by multiplying the number of moderate-to-severe HFs by their severity to determine the HF (mod/sev) index score, using the following formula: HFSSmod/sev = (number of moderate hot flashes/day × 2) + (number of severe hot flashes/day x 3). The Average Daily HFSSmod/sev for each week will be calculated by dividing the total of daily HFSSmod/sev by the number of days observations will be recorded in that week. The change in score is of clinical significance, with a lower score representing less moderate to severe hot flashes and a higher score representing a greater number of moderate to severe hot flashes.
Time frame: Baseline to 4 weeks
Population: Analyses were performed using the intent-to-treat (ITT) population. The ITT population was defined as all subjects who received at least one dose of study medication and have an evaluable primary or secondary efficacy measurement after baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 1 | 17.67 Hot flash severity score (HFSS)/day | Standard Deviation 13.87 |
| 100 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 3 | 10.11 Hot flash severity score (HFSS)/day | Standard Deviation 12.81 |
| 100 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 2 | 12.41 Hot flash severity score (HFSS)/day | Standard Deviation 12.58 |
| 100 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 4 | 11.14 Hot flash severity score (HFSS)/day | Standard Deviation 14.23 |
| 100 mg Q-122 | Change in Hot Flash Severity Score | Baseline | 24.91 Hot flash severity score (HFSS)/day | Standard Deviation 10.76 |
| 200 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 4 | 7.89 Hot flash severity score (HFSS)/day | Standard Deviation 10.06 |
| 200 mg Q-122 | Change in Hot Flash Severity Score | Baseline | 20.64 Hot flash severity score (HFSS)/day | Standard Deviation 4.06 |
| 200 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 1 | 10.09 Hot flash severity score (HFSS)/day | Standard Deviation 6.74 |
| 200 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 2 | 9.51 Hot flash severity score (HFSS)/day | Standard Deviation 7.41 |
| 200 mg Q-122 | Change in Hot Flash Severity Score | Treatment - Week 3 | 9.35 Hot flash severity score (HFSS)/day | Standard Deviation 8.73 |
Secondary
Percent Change in Hot Flash Severity Score
For moderate-to-severe (mod/sev) hot flashes (HF), a score will be calculated by multiplying the number of moderate-to-severe HFs by their severity to determine the HF (mod/sev) index score, using the following formula: HFSSmod/sev = (number of moderate hot flashes/day × 2) + (number of severe hot flashes/day x 3). The Average Daily HFSSmod/sev for each week will be calculated by dividing the total of daily HFSSmod/sev by the number of days observations will be recorded in that week.
Time frame: Baseline to 4 weeks
Population: Analyses were performed using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 mg Q-122 | Percent Change in Hot Flash Severity Score | -61.97 Percent change | Standard Deviation 36.03 |
| 200 mg Q-122 | Percent Change in Hot Flash Severity Score | -67.55 Percent change | Standard Deviation 40.81 |
Secondary
Symptoms Associated With Postmenopausal Status
Greene Climacteric Scale: A comprehensive assessment divided into psychological, physical and vasomotor areas. The scale includes 21 symptoms, subject will score the severity of each symptom with the following score system: 0 = not at all; 1 = a little; 2 = quite a bit; and 3 = extremely. The results represent the total combined score, which can range from 0 to 63. A lower score represents a better outcome.
Time frame: Baseline and 4 weeks
Population: Analyses were performed using the intent-to-treat (ITT) population. The ITT population was defined as all subjects who received at least one dose of study medication and had an evaluable primary or secondary efficacy measurement after baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg Q-122 | Symptoms Associated With Postmenopausal Status | Total Score - Baseline | 18.1 score on a scale | Standard Deviation 6.15 |
| 100 mg Q-122 | Symptoms Associated With Postmenopausal Status | Total Score - 4 weeks | 6.5 score on a scale | Standard Deviation 5.95 |
| 200 mg Q-122 | Symptoms Associated With Postmenopausal Status | Total Score - Baseline | 19.1 score on a scale | Standard Deviation 12.38 |
| 200 mg Q-122 | Symptoms Associated With Postmenopausal Status | Total Score - 4 weeks | 4.5 score on a scale | Standard Deviation 2.88 |