A Phase 2A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of ACER-801 for Treatment of Moderate to Severe Vasomotor Symptoms (VMS) Associated With Menopause
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration (Cmax) of ACER-801
研究概览
简要总结
In this clinical research study, subjects will be given the study drug, ACER-801 (osanetant) or placebo (looks like the study drug but contains no active ingredients). The study drug works on a receptor in the brain and the intended purpose is for the study treatment of moderate to severe Vasomotor Symptoms (VMS) also referred to as hot flashes or flushes associated with menopause. Hot flashes are a change in your temperature that occurs due to changes in your hormones.
详细描述
This is a Phase 2a, randomized, double-blind, placebo-controlled, dose-ranging study in post menopausal women in which the pharmacokinetics, safety and efficacy of ACER-801 (osanetant 50 mg twice daily [BID], 100 mg BID, and 200 mg BID) will be compared to placebo.
Subjects will enter a Screening Period to determine eligibility. Subjects will be required to complete hot flash diaries for 2 weeks prior to randomization. Eligible subjects will be admitted to a Clinical Research Unit and remain in the clinic for 14 days after completion of treatment and all study assessments. The study includes a 14 day safety follow-up assessment. Subjects will be randomized in a 1:1:1:1 ratio.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The patient, the Investigator, and other members of the staff involved with the study will remain blinded to study treatment.
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Post-menopausal female subjects 40-65 years of age, inclusive.
- •Menopause will be defined as:
- •At least 12 months of spontaneous, continuous amenorrhea, or
- •At least 6 months of spontaneous, continuous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL at screening, or
- •At least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
- •At baseline women:
- •With an average number of moderate to severe hot flashes/day for 2 weeks prior to randomization (per continuous hot flash diary).
- •That have a change of < 50% in average 24-hour hot flash frequency 2 weeks prior to randomization.
- •Moderate: defined as sensation of heat with sweating, able to continue activity.
- •Severe: defined as sensation of heat with sweating, causing cessation of activity.
排除标准
- •Any active comorbid disease deemed by the investigator to be clinically significant, which could impact safety during study conduct including renal or hepatic impairment.
- •Use of any prohibited medications.
- •Body mass index (BMI) >35 kg/m
- •Any active ongoing condition that could cause difficulty in interpreting vasomotor symptoms.
- •Inability to complete questionnaires and continuous hot flash diary for any reason.
- •Subjects who, in the opinion of the investigator, should not participate in the study for any other reason.
研究组 & 干预措施
ACER-801 50 mg BID
ACER-801 (osanetant) 50 mg BID (1 x 50 mg and 3 x placebo, twice daily)
干预措施: ACER-801 50 mg BID (Drug)
ACER-801 100 mg BID
ACER-801 (osanetant) 100 mg BID (2 x 50 mg and 2 x placebo, twice daily)
干预措施: ACER-801 100 mg BID (Drug)
ACER-801 200 mg BID
ACER-801 (osanetant) 200 mg BID (4 x 50 mg and 0 x placebo, twice daily)
干预措施: ACER-801 200 mg BID (Drug)
Placebo
Placebo (4 x Placebo of ACER-801 twice daily)
干预措施: Placebo (Drug)
结局指标
主要结局
Peak Plasma Concentration (Cmax) of ACER-801
时间窗: Day 14
maximum concentration of ACER-801 measured at Day 14 Blood sampling included predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 hrs (prior to evening dose) and 15 hrs post morning dose. Only Cmax (mean, SD) data are available due to abbreviated data analyses.
Peak Plasma Concentration (Cmax) of ACER-801 Metabolite
时间窗: Day 14
peak concentration of ACER-801 metabolite measured at Day 14 Blood sampling included predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 hrs (prior to evening dose) and 15 hrs post morning dose. Only Cmax (mean, SD) data are available due to abbreviated data analyses.
Time to Reach Maximum Concentration (Tmax) of ACER-801
时间窗: Day 14
time to reach maximum concentration of ACER-801 at Day 14 Blood sampling included predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 hrs (prior to evening dose) and 15 hrs post morning dose. Only Tmax (mean, SD) data are available due to abbreviated data analyses.
Time to Reach Maximum Concentration (Tmax) of ACER-801 Metabolite
时间窗: Day 14
Time to reach maximum concentration of ACER-801 metabolite at Day 14 Blood sampling included predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 hrs (prior to evening dose) and 15 hrs post morning dose. Only Tmax (mean, SD) data are available due to abbreviated data analyses.
Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801
时间窗: Day 14
Area under the concentration time curve (AUC) from the time of dosing (0 hour) to the time of the last quantifiable (positive) concentration (Tlast) of ACER-801, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method) Blood sampling included predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 hrs (prior to evening dose) and 15 hrs post morning dose. Only AUClast (mean, SD) data are available due to abbreviated data analyses.
Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801 Metabolite
时间窗: Day 14
Area under the concentration time curve (AUC) from the time of dosing (0 hour) to the time of the last quantifiable (positive) concentration (Tlast) of ACER-801 metabolite, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method) Blood sampling included predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 hrs (prior to evening dose) and 15 hrs post morning dose. Only AUClast (mean, SD) data are available due to abbreviated data analyses.
Half-life (T1/2) of ACER-801
时间窗: Day 14
Terminal elimination half-life of ACER-801
Half-life (T1/2) of ACER-801 Metabolite
时间窗: Day 14
Terminal elimination half-life of ACER-801 metabolite
Number and Percentage of Adverse Events ≥ 5%
时间窗: 2 weeks
An Adverse Event (AE) is defined as any untoward medical occurrence associated with the use of the investigational product in humans, whether or not considered related to investigational product. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with any use of the investigational product, without any judgment about causality and irrespective of route of administration, formulation, or dose, including an overdose.
Number and Percentage of Serious Adverse Events (SAE)
时间窗: 2 weeks
An AE is considered "serious" if, in the view of either the investigator or Acer, it results in any of the following outcomes: Death, Is immediately life threatening; Requires in-patient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability or incapacity; Results in a congenital abnormality or birth defect; Is an important medical event that may jeopardize the subject or may require medical intervention to prevent one of the outcomes listed above.
Number and Percentage of Subjects Who Discontinued From the Study
时间窗: Over 2 weeks
Discontinuation or withdrawal from the study.
Number of Patients With a Clinically Significant Change From Baseline in Abnormalities Detected During Physical Examination
时间窗: At Day 14 relative to Baseline
A physician or appropriately qualified delegate conducted a full physical examination at baseline and at Day 14. The investigator decides if findings are considered abnormal at baseline and at Day 14 and whether the change is clinically significant. Only clinically significant changes will be reported.
Accumulation Ratio for Cmax (ARcmax) of ACER-801
时间窗: Day 14
Cmax (maximum concentration) Accumulation Ratio calculated as Cmax,Day14/ Cmax,Day1 and AUCt,Day14/ AUCt,Day1, where the dosing interval t is 12h.
Accumulation Ratio for AUC (ARauc) of ACER-801
时间窗: Day 14
AUC (area under the curve) Accumulation Ratio calculated as Cmax,Day14/ Cmax,Day1 and AUCt,Day14/ AUCt,Day1, where the dosing interval t is 12h.
Accumulation Ratio for Cmax (ARcmax) of ACER-801 Metabolite
时间窗: Day 14
Cmax (maximum concentration) Accumulation Ratio calculated as Cmax,Day14/ Cmax,Day1 and AUCt,Day14/ AUCt,Day1, where the dosing interval t is 12h.
Accumulation Ratio for AUC (ARauc) of ACER-801 Metabolite
时间窗: Day 14
AUC (area under the curve) Accumulation Ratio calculated as Cmax,Day14/ Cmax,Day1 and AUCt,Day14/ AUCt,Day1, where the dosing interval t is 12h.
Metabolite: Parent Ratio of AUC (MRauc)
时间窗: Day 14
AUC (area under the curve) MR = Metabolite:Parent Ratio calculated as Cm,day14/ Cp,day1 and AUCt,m,day14/ AUCt,p,day1, where m and p are the metabolite and parent drug, respectively, and t is the dosing interval (12 h).
Metabolite:Parent Ratio of Cmax (MRcmax)
时间窗: Day 14
MR = Metabolite:Parent Ratio calculated as Cm,day14/ Cp,day1 and AUCt,m,day14/ AUCt,p,day1, where m and p are the metabolite and parent drug, respectively, and t is the dosing interval (12 h). ACER-801 (parent); Cmax (maximum concentration)
Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801
时间窗: Day 14
AUC from the time of dosing (0 hour) extrapolated to infinity, calculated as AUClast + Clast/λz, where Clast was the last quantifiable concentration, and λz was the terminal elimination rate constant Reliability of AUCinf values was contingent upon AUCext and λz Profiles with AUCext ≤20% and a λz which met reporting criteria were considered reliable and AUCinf was reported. For profiles that did not meet these criteria, AUCinf and any parameter requiring AUCinf for computation were not reported.
Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801 Metabolite
时间窗: Day 14
AUC from the time of dosing (0 hour) extrapolated to infinity, calculated as AUClast + Clast/λz, where Clast was the last quantifiable concentration, and λz was the terminal elimination rate constant Reliability of AUCinf values was contingent upon AUCext and λz Profiles with AUCext ≤20% and a λz which met reporting criteria were considered reliable and AUCinf was reported. For profiles that did not meet these criteria, AUCinf and any parameter requiring AUCinf for computation were not reported.
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: HEMATOLOGY
时间窗: Over 2 weeks
Blood samples will be measured for hemoglobin, hematocrit, white blood count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count, red blood cell count (including mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration). Only clinically significant changes will be reported.
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: SERUM CHEMISTRY
时间窗: 2 weeks
Blood samples will be measured for albumin, alkaline phosphatase, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, calcium, carbon dioxide, chloride, potassium, sodium, total cholesterol, creatinine, gamma glutamyl transferase, glucose, lactate dehydrogenase, phosphorus, total protein, uric acid. Only clinically significant changes will be reported.
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: COAGULATION
时间窗: 2 weeks
Blood samples will be measured for prothrombin time, partial thromboplastin time, international normalized ratio. Only clinically significant changes will be reported.
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: URINALYSIS
时间窗: 2 weeks
Urine samples will be measured for pH, specific gravity, protein, glucose, ketones, bilirubin. Only clinically significant changes will be reported.
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: BONE DENSITY MARKERS
时间窗: 2 weeks
Blood samples not available/collected for testing. Blood samples will be measured for Bone Specific Alkaline Phosphatase (BSAP), osteocalcin, amino terminal propeptide of type 1 collagen (P1NP) and Collagen Type- C-Telopeptide (CTX). Only clinically significant changes will be reported.
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: HORMONES
时间窗: 2 weeks
Blood samples not available/collected for testing. Blood samples will be measured for catecholamines, vasopressin, gonadotropins, estradiol, testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), T3 (Total and Free), T4 (Total and Free), prolactin, sex hormone binding globulin (SHBG), and insulin. Only clinically significant changes will be reported.
次要结局
- Change in Frequency of Vasomotor Symptoms (Hot Flashes) From Baseline(At Week 1 relative to Baseline)
- Change in Frequency Vasomotor Symptoms (Hot Flashes) From Baseline(At Week 2 relative to Baseline)
- Change in Severity of Vasomotor Symptoms (Hot Flashes) From Baseline(At Week 2 relative to Baseline)
- Change in Hot Flash Severity Score Vasomotor Symptoms From Baseline(At Week 1 relative to Baseline)
- Change in Hot Flash Severity Score of Vasomotor Symptoms From Baseline(At Week 2 relative to Baseline)