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

NCT05325775 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ACER-801-201
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Post-menopausal Vasomotor Symptoms

Outcome Measures

Primary Outcomes (38)

• 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 Outcomes (6)

• 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 1 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

Study Arms (4)

ACER-801 50 mg BID

EXPERIMENTAL

ACER-801 (osanetant) 50 mg BID (1 x 50 mg and 3 x placebo, twice daily)

Drug: ACER-801 50 mg BID

ACER-801 100 mg BID

EXPERIMENTAL

ACER-801 (osanetant) 100 mg BID (2 x 50 mg and 2 x placebo, twice daily)

Drug: ACER-801 100 mg BID

ACER-801 200 mg BID

EXPERIMENTAL

ACER-801 (osanetant) 200 mg BID (4 x 50 mg and 0 x placebo, twice daily)

Drug: ACER-801 200 mg BID

Placebo

PLACEBO COMPARATOR

Placebo (4 x Placebo of ACER-801 twice daily)

Drug: Placebo

Interventions

ACER-801 50 mg BID DRUG

50 mg BID (twice daily)

Also known as: osanetant

ACER-801 50 mg BID

ACER-801 100 mg BID DRUG

100 mg BID (twice daily)

Also known as: osanetant

ACER-801 100 mg BID

ACER-801 200 mg BID DRUG

200 mg BID (twice daily)

Also known as: osanetant

ACER-801 200 mg BID

Placebo DRUG

Placebo

Also known as: Placebo of ACER-801

Placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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/m2.
• 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.

Sponsors & Collaborators

• Acer Therapeutics Inc.: lead

Study Sites (1)

Spaulding Clinical Research

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Interventions

BID protein, human; SR 142801

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Acer Therapeutics Inc ( a wholly owned subsidiary of Zevra Therapeutics Inc

aquartel@zevra.com

844-902-6100

Study Officials

• Jennifer Boston, MSN, APNP

  Spaulding Clinical Research LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The patient, the Investigator, and other members of the staff involved with the study will remain blinded to study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 1:1:1:1 ratio to ACER-801 per one of the following dosing schedules prior to dosing: * 50 mg BID, * 100 mg BID, * 200 mg BID, or * Placebo BID Each arm is administered orally for 14 consecutive days (28 doses).

Study Record Dates

• First Submitted: March 27, 2022
• First Posted: April 13, 2022
• Study Start: March 30, 2022
• Primary Completion: March 4, 2023
• Study Completion: March 4, 2023
• Last Updated: August 7, 2024
• Results First Posted: August 7, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)