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

Post-menopausal Vasomotor Symptoms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05325775
• Other study ID #: ACER-801-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 30, 2022
• Est. completion date: March 4, 2023

Study information

• Verified date: April 2023
• Source: Acer Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 4, 2023
• Est. primary completion date: March 4, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Post-menopausal Vasomotor Symptoms

Intervention

Drug:
• ACER-801 50 mg BID
50 mg BID (twice daily)
• ACER-801 100 mg BID
100 mg BID (twice daily)
• ACER-801 200 mg BID
200 mg BID (twice daily)
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Spaulding Clinical Research	West Bend	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Acer Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Plasma Concentration (Cmax) of ACER-801	maximum concentration of ACER-801	Day 1, Day 14
Primary	Time to reach maximum concentration (tmax) of ACER-801		Day 1, Day 14
Primary	Area under the concentration curve from dosing to the time of the last measured concentration (AUClast) of ACER-801		Day 1, Day 14
Primary	Area under the concentration curve from t0 to infinite time (AUCinf) of ACER-801		Day 1, Day 14
Primary	Metabolite:parent ratio of Cmax (MRCmax) of ACER-801	ACER-801 (parent); Cmax (maximum concentration)	Day 1, Day 14
Primary	Metabolite:parent ratio of AUC (MRauc) of ACER-801	ACER-801 (parent); AUC (area under the curve)	Day 1, Day 14
Primary	Half-life (t1/2) of ACER-801		Day 1, Day 14
Primary	Accumulation ratio for Cmax (ARcmax) of ACER-801	Cmax (maximum concentration)	Day 14
Primary	Accumulation ratio for AUC (ARcauc) of ACER-801	AUC (area under the curve)	Day 14
Primary	Peak Plasma Concentration (Cmax) of ACER-801 metabolite		Day 1, Day 14
Primary	Time to reach maximum concentration (tmax) of ACER-801 metabolite		Day 1, Day 14
Primary	Area under the concentration curve from dosing to the time of the last measured concentration (AUClast) of ACER-801 metabolite		Day 1, Day 14
Primary	Area under the concentration curve from t0 to infinite time (AUCinf) of ACER-801 metabolite		Day 1, Day 14
Primary	Metabolite:parent ratio of Cmax (MRcmax) of ACER-801 metabolite	ACER-801 (parent); Cmax (maximum concentration)	Day 1, Day 14
Primary	Accumulation ratio for AUC (MRauc) of ACER-801 metabolite	AUC (area under the curve)	Day 1, Day 14
Primary	Half-life (t1/2) of ACER-801 metabolite		Day 1, Day 14
Primary	Accumulation ratio for Cmax (ARcmax) of ACER-801 metabolite	Cmax (maximum concentration)	Day 14
Primary	Accumulation ratio for AUC (ARcauc) of ACER-801 metabolite	AUC (area under the curve)	Day 14
Primary	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
Primary	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.	Over 2 weeks
Primary	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.	Over 2 weeks
Primary	Number and percentage of subjects who discontinued from the study	Discontinuation or withdrawal from the study.	Over 2 weeks
Primary	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
Primary	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.	Over 2 weeks
Primary	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.	Over 2 weeks
Primary	Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: HORMONES	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.	Over 2 weeks
Primary	Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: BONE DENSITY MARKERS	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.	Over 2 weeks
Primary	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.	Over 2 weeks
Secondary	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.	At Week 1 and Week 2 relative to Baseline
Secondary	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.	At Week 1 and Week 2 relative to Baseline
Secondary	Change in severity score vasomotor symptoms (hot flashes) 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].; Higher scores mean greater severity of hot flashes.	At Week 1 and Week 2 relative to Baseline