This is a Phase 2 proof-of-concept (POC) study designed to determine the effectiveness of
Q-122 for the treatment of Vasomotor Symptoms (VMS) versus placebo. Participants who meet all
eligibility criteria following the Screening/Run-In period will be randomized to 1 of 2
treatment arms; blinded Q-122 or placebo for a period of 28 days. All participants will be
followed for a 2-week, drug-free, follow-up period after their last dose of blinded
Q-122/placebo before termination from the study.
Vasomotor symptoms (VMS) 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 often contraindicated and is
not an option for women receiving endocrine therapy including tamoxifen (TAM) and aromatase
inhibitors (AI). Breast cancer survivors, and women receiving endocrine therapy in
particular, have a high rate of problematic hot flashes. In an open label Phase 1 study of
the safety and activity of Q-122 in breast cancer patients taking TAM or an AI, 8 of 9 women
who received at least 1 dose of 100 mg and 10 of 11 women who received at least 1 dose of 200
mg had a reduction in hot flashes of 2 or more per day, the FDA criteria for anti-VMS
activity. This study will define the effect of Q-122 versus placebo in a population of women
with a history of or current breast cancer who have an average of 50 or more moderate to
severe hot flashes per week.
Inclusion Criteria:
1. Be a female, aged between 18 - 70 years on the day of informed consent.
2. Have a history of or current breast cancer and currently taking tamoxifen or an
aromatase inhibitor.
3. On a stable dose of TAM or an AI for a minimum of 30 days before the Screening Visit
and no anticipated need to change the dose for the duration of the study.
4. Experience an average of at least 50 moderate to severe hot flashes/week for the 2
weeks immediately preceding the Run-In Visit (i.e., during the Screening period).
5. If on thyroid medication, on a stable dose for a minimum of 30 days before the
Screening Visit and no anticipated need to change the dose for the duration of the
study.
6. Willing and able to complete the daily participant diary, attend all study visits, and
participate in all study procedures.
7. Able to provide informed consent.
Exclusion Criteria:
1. Childbearing potential, pregnancy, or lactation except in patients who are on stable
dose of AI in combination with luteinizing hormone releasing hormone agonists such as
Zoladex, Leuprolide (Lupron) or equivalent. Non-childbearing potential is defined as
physiologically incapable of becoming pregnant by one of the following:
- Has had a partial or complete hysterectomy or
- Has had a bilateral oophorectomy or
- Has had a bilateral tubal ligation or fallopian tube inserts or
- Is post-menopausal (amenorrhea > 1 year) confirmed by levels of follicle
stimulating hormone (FSH). FSH levels may be lower in menopausal women treated
with tamoxifen when compared with FSH levels appropriate for confirming menopause
in women not treated with tamoxifen. For those patients who are on stable dose of
tamoxifen, confirmation of menopause is based on the clinical opinion of the PI
and medical monitor on a 'case-by-case basis'.
2. Currently experiencing undiagnosed vaginal bleeding.
3. Women with advanced breast cancer (Stage 4).
4. Greater than 60% reduction in the frequency of moderate to severe hot flashes during
the 1-week single blind Run-In period or inability to correctly record hot flashes
and/or drug dosing in the participant diary.
5. Participation in another clinical or surgical trial within 30 days prior to screening
or during the study without the prior written consent of the Medical Monitor.
6. Gastrointestinal, liver, kidney or other conditions which could interfere with the
absorption, distribution, metabolism or excretion of Q-122 at PI discretion.
7. Untreated overt hyperthyroidism.
8. Have any other medical condition, clinically important systemic disease or significant
co-morbidities or any finding during Screening that in the judgment of the
investigator puts the participant at increased risk by participation in this study, or
that may affect the reliability of participant diary entries.
9. Known inability to complete all study visits and study assessments for scheduling or
other reasons.
10. BMI > 40 kg/m2; Participants with a BMI greater than 40 kg/m2 may be enrolled on a
case-by-case basis if approved by the Medical Monitor and if the participant is not
deemed at increased risk of adverse effects based on body habitus and cardiovascular
health.
11. Women with a history of, or current evidence of, abuse of alcohol or any drug
substance, or who regularly drink more than 3 standard drinks per day.
12. Uncontrolled systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg on
3 consecutive readings within the screening visit.
13. Abnormal laboratory findings:
1. Hemoglobin < 9.5 g/dL (g/L); or any abnormal values that are deemed clinically
significant by the investigator should be discussed with the medical monitor
before being deemed ineligible.
2. Fasting ALT, AST, GGT, or bilirubin greater than twice the upper limit of normal
that is confirmed on a second sample.
3. <60 eGFR mL/min/1.73 m2.
14. In the opinion of the investigator, have substantial risk of disease progression
within the 3 months following screening and/or who potentially may require further
treatment for their breast cancer during the study period including follow-up.
15. Any other reason which in the investigator's opinion makes the participant unsuitable
for a clinical trial.
16. On any medications, either prescription or over-the-counter that are being taken
solely for the purpose of treating VMS including SSRI/SNRI, gabapentin or pregabalin.
