Clinical trial NCT05325775: Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Post-menopausal Vasomotor Symptoms
Lead sponsor: Acer Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-13
Enrollment: 49
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peak Plasma Concentration (Cmax) of ACER-801
timeFrame: Day 1
measure: Peak Plasma Concentration (Cmax) of ACER-801
timeFrame: Day 14
measure: Peak Plasma Concentration (Cmax) of ACER-801 Metabolite
timeFrame: Day 1
measure: Peak Plasma Concentration (Cmax) of ACER-801 Metabolite
timeFrame: Day 14
measure: Time to Reach Maximum Concentration (Tmax) of ACER-801
timeFrame: Day 1
measure: Time to Reach Maximum Concentration (Tmax) of ACER-801
timeFrame: Day 14
measure: Time to Reach Maximum Concentration (Tmax) of ACER-801 Metabolite
timeFrame: Day 1
measure: Time to Reach Maximum Concentration (Tmax) of ACER-801 Metabolite
timeFrame: Day 14
measure: Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801
timeFrame: Day 1
measure: Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801
timeFrame: Day 14
measure: Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801 Metabolite
timeFrame: Day 1
measure: Area Under the Concentration Curve From Dosing to the Time of the Last Measured Concentration (AUClast) of ACER-801 Metabolite
timeFrame: Day 14
measure: Half-life (T1/2) of ACER-801
timeFrame: Day 1
measure: Half-life (T1/2) of ACER-801
timeFrame: Day 14
measure: Half-life (T1/2) of ACER-801 Metabolite
timeFrame: Day 1
measure: Half-life (T1/2) of ACER-801 Metabolite
timeFrame: Day 14
measure: Number and Percentage of Adverse Events ≥ 5%
timeFrame: 2 weeks
measure: Number and Percentage of Serious Adverse Events (SAE)
timeFrame: 2 weeks
measure: Number and Percentage of Subjects Who Discontinued From the Study
timeFrame: Over 2 weeks
measure: Number of Patients With a Clinically Significant Change From Baseline in Abnormalities Detected During Physical Examination
timeFrame: At Day 14 relative to Baseline
measure: Accumulation Ratio for Cmax (ARcmax) of ACER-801
timeFrame: Day 14
measure: Accumulation Ratio for AUC (ARauc) of ACER-801
timeFrame: Day 14
measure: Accumulation Ratio for Cmax (ARcmax) of ACER-801 Metabolite
timeFrame: Day 14
measure: Accumulation Ratio for AUC (ARauc) of ACER-801 Metabolite
timeFrame: Day 14
measure: Metabolite: Parent Ratio of AUC (MRauc)
timeFrame: Day 1
measure: Metabolite: Parent Ratio of AUC (MRauc)
timeFrame: Day 14
measure: Metabolite:Parent Ratio of Cmax (MRcmax)
timeFrame: Day 1
measure: Metabolite:Parent Ratio of Cmax (MRcmax)
timeFrame: Day 14
measure: Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801
timeFrame: Day 1
measure: Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801
timeFrame: Day 14
measure: Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801 Metabolite
timeFrame: Day 1
measure: Area Under the Concentration Curve From t0 to Infinite Time (AUCinf) of ACER-801 Metabolite
timeFrame: Day 14
measure: Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: HEMATOLOGY
timeFrame: Over 2 weeks
measure: Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: SERUM CHEMISTRY
timeFrame: 2 weeks
measure: Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: COAGULATION
timeFrame: 2 weeks
measure: Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: URINALYSIS
timeFrame: 2 weeks
measure: Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: BONE DENSITY MARKERS
timeFrame: 2 weeks
measure: Number of Subjects With a Clinically Significant Change From Baseline for Clinical Laboratory Evaluations: HORMONES
timeFrame: 2 weeks
Secondary outcomes:
measure: Change in Frequency of Vasomotor Symptoms (Hot Flashes) From Baseline
timeFrame: At Week 1 relative to Baseline
measure: Change in Frequency Vasomotor Symptoms (Hot Flashes) From Baseline
timeFrame: At Week 2 relative to Baseline
measure: Change in Severity of Vasomotor Symptoms (Hot Flashes) From Baseline
timeFrame: At Week 1 relative to Baseline
measure: Change in Severity of Vasomotor Symptoms (Hot Flashes) From Baseline
timeFrame: At Week 2 relative to Baseline
measure: Change in Hot Flash Severity Score Vasomotor Symptoms From Baseline
timeFrame: At Week 1 relative to Baseline
measure: Change in Hot Flash Severity Score of Vasomotor Symptoms From Baseline
timeFrame: At Week 2 relative to Baseline
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical Research
state: Wisconsin
Study officials:
affiliation: Spaulding Clinical Research LLC
name: Jennifer Boston, MSN, APNP
role: PRINCIPAL_INVESTIGATOR
References: