Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause

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

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.

Study Overview

• Status: Completed
• Conditions: Post-menopausal Vasomotor Symptoms
• Intervention / Treatment: Drug: Placebo; Drug: ACER-801 50 mg BID; Drug: ACER-801 100 mg BID; Drug: ACER-801 200 mg BID

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Post-menopausal female subjects 40-65 years of age, inclusive.

   Menopause will be defined as:

   1. At least 12 months of spontaneous, continuous amenorrhea, or
   2. At least 6 months of spontaneous, continuous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL at screening, or
   3. At least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.

2. At baseline women:

   1. With an average number of moderate to severe hot flashes/day for 2 weeks prior to randomization (per continuous hot flash diary).

   2. 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.

Key Exclusion Criteria:

1. Any active comorbid disease deemed by the investigator to be clinically significant, which could impact safety during study conduct including renal or hepatic impairment.
2. Use of any prohibited medications.
3. Body mass index (BMI) >35 kg/m2.
4. Any active ongoing condition that could cause difficulty in interpreting vasomotor symptoms.
5. Inability to complete questionnaires and continuous hot flash diary for any reason.
6. Subjects who, in the opinion of the investigator, should not participate in the study for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACER-801 50 mg BID; ACER-801 (osanetant) 50 mg BID (1 x 50 mg and 3 x placebo, twice daily)	Drug: ACER-801 50 mg BID; 50 mg BID (twice daily); Other Names: osanetant
Experimental: ACER-801 100 mg BID; ACER-801 (osanetant) 100 mg BID (2 x 50 mg and 2 x placebo, twice daily)	Drug: ACER-801 100 mg BID; 100 mg BID (twice daily); Other Names: osanetant
Placebo Comparator: Placebo; Placebo (4 x Placebo of ACER-801 twice daily)	Drug: Placebo; Placebo; Other Names: Placebo of ACER-801
Experimental: ACER-801 200 mg BID; ACER-801 (osanetant) 200 mg BID (4 x 50 mg and 0 x placebo, twice daily)	Drug: ACER-801 200 mg BID; 200 mg BID (twice daily); Other Names: osanetant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax) of ACER-801	maximum concentration of ACER-801 measured at Day 1 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.	Day 1
Peak Plasma Concentration (Cmax) of ACER-801	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.	Day 14
Peak Plasma Concentration (Cmax) of ACER-801 Metabolite	peak concentration of ACER-801 metabolite measured at Day 1 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.	Day 1
Peak Plasma Concentration (Cmax) of ACER-801 Metabolite	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.	Day 14
Time to Reach Maximum Concentration (Tmax) of ACER-801	time to reach maximum concentration of ACER-801 measured at Day 1 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.	Day 1
Time to Reach Maximum Concentration (Tmax) of ACER-801	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.	Day 14
Time to Reach Maximum Concentration (Tmax) of ACER-801 Metabolite	time to reach maximum concentration of ACER-801 metabolite at Day 1 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.	Day 1
Time to Reach Maximum Concentration (Tmax) of ACER-801 Metabolite	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.	Day 14
Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801	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.	Day 1
Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801	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.	Day 14
Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801 Metabolite	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.	Day 1
Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801 Metabolite	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.	Day 14
Half-life (T1/2) of ACER-801	Terminal elimination half-life of ACER-801	Day 1
Half-life (T1/2) of ACER-801	Terminal elimination half-life of ACER-801	Day 14
Half-life (T1/2) of ACER-801 Metabolite	Terminal elimination half-life of ACER-801 metabolite	Day 1
Half-life (T1/2) of ACER-801 Metabolite	Terminal elimination half-life of ACER-801 metabolite	Day 14
Number and Percentage of Adverse Events ≥ 5%	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.	2 weeks
Number and Percentage of Serious Adverse Events (SAE)	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.	2 weeks
Number and Percentage of Subjects Who Discontinued From the Study	Discontinuation or withdrawal from the study.	Over 2 weeks
Number of Patients With a Clinically Significant Change From Baseline in Abnormalities Detected During Physical Examination	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.	At Day 14 relative to Baseline
Accumulation Ratio for Cmax (ARcmax) of ACER-801	Cmax (maximum concentration) Accumulation Ratio calculated as Cmax,Day14/ Cmax,Day1 and AUCt,Day14/ AUCt,Day1, where the dosing interval t is 12h.	Day 14
Accumulation Ratio for AUC (ARauc) of ACER-801	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.	Day 14
Accumulation Ratio for Cmax (ARcmax) of ACER-801 Metabolite	Cmax (maximum concentration) Accumulation Ratio calculated as Cmax,Day14/ Cmax,Day1 and AUCt,Day14/ AUCt,Day1, where the dosing interval t is 12h.	Day 14
Accumulation Ratio for AUC (ARauc) of ACER-801 Metabolite	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.	Day 14
Metabolite: Parent Ratio of AUC (MRauc)	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). AUC = area under the curve	Day 1
Metabolite: Parent Ratio of AUC (MRauc)	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).	Day 14
Metabolite:Parent Ratio of Cmax (MRcmax)	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)	Day 1
Metabolite:Parent Ratio of Cmax (MRcmax)	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)	Day 14
Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801	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.	Day 1
Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801	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.	Day 14
Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801 Metabolite	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.	Day 1
Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801 Metabolite	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.	Day 14
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: HEMATOLOGY	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.	Over 2 weeks
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: SERUM CHEMISTRY	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.	2 weeks
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: COAGULATION	Blood samples will be measured for prothrombin time, partial thromboplastin time, international normalized ratio. Only clinically significant changes will be reported.	2 weeks
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: URINALYSIS	Urine samples will be measured for pH, specific gravity, protein, glucose, ketones, bilirubin. Only clinically significant changes will be reported.	2 weeks
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: BONE DENSITY MARKERS	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.	2 weeks
Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: HORMONES	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.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Frequency of Vasomotor Symptoms (Hot Flashes) From Baseline	Frequency is the number of vasomotor symptoms (hot flashes) recorded by the subject in the continuous diary. Week 1	At Week 1 relative to Baseline
Change in Frequency Vasomotor Symptoms (Hot Flashes) From Baseline	Frequency is the number of vasomotor symptoms (hot flashes) recorded by the subject in the continuous diary. Week 2	At Week 2 relative to Baseline
Change in Severity of Vasomotor Symptoms (Hot Flashes) From Baseline	Patients recorded in a continuous diary the number of individual hot flashes experienced and rated the severity of each on a scale of mild, moderate, or severe where mild is assigned a value of 1, moderate a value of 2, and severe a value of 3 during data analysis. Daily severity was calculated as [(1 × number of mild hot flashes) + (2 × number of moderate hot flashes) + (3 × number of severe hot flashes)]/total number of hot flashes reported. The value at Week 1 was subtracted from the value at Baseline to yield the impact on severity score. A negative change indicates a reduction in severity.	At Week 1 relative to Baseline
Change in Severity of Vasomotor Symptoms (Hot Flashes) From Baseline	Patients recorded in a continuous diary the number of individual hot flashes experienced and rated the severity of each on a scale of mild, moderate, or severe where mild is assigned a value of 1, moderate a value of 2, and severe a value of 3 during data analysis. Daily severity was calculated as [(1 × number of mild hot flashes) + (2 × number of moderate hot flashes) + (3 × number of severe hot flashes)]/total number of hot flashes reported. The value at Week 2 was subtracted from the value at Baseline to yield the impact on severity score. A negative change indicates a reduction.	At Week 2 relative to Baseline
Change in Hot Flash Severity Score Vasomotor Symptoms From Baseline	The hot flash severity score is a composite of the frequency and severity of hot flashes, and was calculated as follows: [number of mild hot flashes on Day Y x 1] + [number of moderate hot flashes on Day Y x 2] + [number of severe hot flashes on Day Y x 3]. The value at Week 1 was subtracted from the value at Baseline to yield the impact on the composite hot flash severity score. A negative change indicates a reduction.	At Week 1 relative to Baseline
Change in Hot Flash Severity Score of Vasomotor Symptoms From Baseline	The hot flash severity score is a composite of the frequency and severity of hot flashes, and was calculated as follows: [number of mild hot flashes on Day Y x 1] + [number of moderate hot flashes on Day Y x 2] + [number of severe hot flashes on Day Y x 3]. The value at Week 2 was subtracted from the value at Baseline to yield the impact on hot flash severity score. A negative change indicates a reduction in severity.	At Week 2 relative to Baseline

Collaborators and Investigators

• Sponsor: Acer Therapeutics Inc.
• Investigators: Principal Investigator: Jennifer Boston, MSN, APNP, Spaulding Clinical Research LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Actual): March 4, 2023
• Study Completion (Actual): March 4, 2023

Study Registration Dates

• First Submitted: March 27, 2022
• First Submitted That Met QC Criteria: April 6, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; SR 142801
• Other Study ID Numbers: ACER-801-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No