Trial Outcomes & Findings for Neuropeptide Treatment for Hot Flushes During the Menopause (NCT NCT02668185)
NCT ID: NCT02668185
Last Updated: 2021-05-03
Results Overview
To ensure accurate records, participants recorded their flushes in real time using either a tally chart on a piece of paper (n=34) or an application on their smartphone such as Tally Counter (Pixel Research Labs, Minneapolis-Saint Paul, MN, USA; n=3), and then collated their total number of flushes twice daily on waking to record previous overnight symptoms and before bed to record daytime symptoms.
COMPLETED
PHASE2
37 participants
Final week of each 4 week treatment period
2021-05-03
Participant Flow
Participant milestones
| Measure |
Active Drug First Then Placebo
2 week baseline period First NK3R antagonist - AZD4901 - 40mg orally bd - for 4 weeks intervention then 2 weeks washout period then second intervention with Matched placebo orally bd for 4 weeks with 2 weeks monitoring period
|
Placebo First Then Active Drug
2 week baseline period First intervention is Placebo - 40mg bd - for 4 weeks, then 2 weeks washout period, then second intervention with NK3R antagonist - AZD4901 - 40mg orally bd - for 4 weeks with 2 weeks monitoring period
|
|---|---|---|
|
Baseline Period (2 Weeks)
STARTED
|
20
|
17
|
|
Baseline Period (2 Weeks)
COMPLETED
|
20
|
17
|
|
Baseline Period (2 Weeks)
NOT COMPLETED
|
0
|
0
|
|
First Intervention (4 Weeks)
STARTED
|
20
|
17
|
|
First Intervention (4 Weeks)
COMPLETED
|
18
|
17
|
|
First Intervention (4 Weeks)
NOT COMPLETED
|
2
|
0
|
|
Washout Period (2 Weeks)
STARTED
|
18
|
17
|
|
Washout Period (2 Weeks)
COMPLETED
|
17
|
15
|
|
Washout Period (2 Weeks)
NOT COMPLETED
|
1
|
2
|
|
Second Intervention (4 Weeks)
STARTED
|
17
|
15
|
|
Second Intervention (4 Weeks)
COMPLETED
|
16
|
12
|
|
Second Intervention (4 Weeks)
NOT COMPLETED
|
1
|
3
|
|
Moitoring Period (2 Weeks)
STARTED
|
16
|
12
|
|
Moitoring Period (2 Weeks)
COMPLETED
|
16
|
12
|
|
Moitoring Period (2 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Active Drug First Then Placebo
2 week baseline period First NK3R antagonist - AZD4901 - 40mg orally bd - for 4 weeks intervention then 2 weeks washout period then second intervention with Matched placebo orally bd for 4 weeks with 2 weeks monitoring period
|
Placebo First Then Active Drug
2 week baseline period First intervention is Placebo - 40mg bd - for 4 weeks, then 2 weeks washout period, then second intervention with NK3R antagonist - AZD4901 - 40mg orally bd - for 4 weeks with 2 weeks monitoring period
|
|---|---|---|
|
First Intervention (4 Weeks)
Physician Decision
|
2
|
0
|
|
Washout Period (2 Weeks)
Adverse Event
|
1
|
0
|
|
Washout Period (2 Weeks)
Physician Decision
|
0
|
2
|
|
Second Intervention (4 Weeks)
Physician Decision
|
1
|
3
|
Baseline Characteristics
Neuropeptide Treatment for Hot Flushes During the Menopause
Baseline characteristics by cohort
| Measure |
Overall Participants
n=37 Participants
Crossover study - all participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
37 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
White British
|
17 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
White European
|
2 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
White Other
|
1 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
White Unspecified
|
1 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Asian, Pakistani
|
1 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Black Carribean
|
5 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Mixed white and black carribean
|
1 Participants
n=93 Participants
|
|
Region of Enrollment
United Kingdom
|
37 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Final week of each 4 week treatment periodPopulation: Whole group intention to treat analysis irrespective of treatment assignment order, adjusted means from crossover analysis with 95% CIs: percentage change in total no. hot flush frequency during final week of 4 week treatment period with MLE4901 and placebo vs with total no. hot flush frequency during the final week of the 2 week baseline period.
To ensure accurate records, participants recorded their flushes in real time using either a tally chart on a piece of paper (n=34) or an application on their smartphone such as Tally Counter (Pixel Research Labs, Minneapolis-Saint Paul, MN, USA; n=3), and then collated their total number of flushes twice daily on waking to record previous overnight symptoms and before bed to record daytime symptoms.
Outcome measures
| Measure |
Active Drug
n=28 Participants
NK3R antagonist - AZD4901 - 40mg bd - for 4 weeks
NK3R antagonist - AZD4901: Neurokinin 3 receptor antagonist
|
Placebo
n=28 Participants
Placebo - 40mg bd - for 4 weeks
Placebo: Placebo
|
|---|---|---|
|
Total Number of Hot Flushes During the Final Week of Each 4 Weeks Treatment Period
|
19.35 hot flushes
Interval 15.99 to 23.42
|
49.01 hot flushes
Interval 40.81 to 58.56
|
SECONDARY outcome
Timeframe: Twice daily, morning and night for 14 weeksScore on a scale - HF severity (rated as 1-nil, 2-mild, 3-moderate, 4-severe, as per Joffe 2014) recorded twice daily (day/night as described above for HF frequency). Scores are summed.
Outcome measures
| Measure |
Active Drug
n=28 Participants
NK3R antagonist - AZD4901 - 40mg bd - for 4 weeks
NK3R antagonist - AZD4901: Neurokinin 3 receptor antagonist
|
Placebo
n=28 Participants
Placebo - 40mg bd - for 4 weeks
Placebo: Placebo
|
|---|---|---|
|
Hot Flush Severity
|
3.27 numerical rating of severity by particip
Interval 2.92 to 3.66
|
5.70 numerical rating of severity by particip
Interval 5.09 to 6.38
|
SECONDARY outcome
Timeframe: twice daily (day/night) for 14 weeksScore on a scale - HF bother (rated as 1-none, 2-a little, 3-moderate, 4-a lot, as per Joffe 2014) will be recorded twice daily (day/night as described above for HF frequency). The data will be analysed as detailed above for the HF frequency. Scores are summed.
Outcome measures
| Measure |
Active Drug
n=28 Participants
NK3R antagonist - AZD4901 - 40mg bd - for 4 weeks
NK3R antagonist - AZD4901: Neurokinin 3 receptor antagonist
|
Placebo
n=28 Participants
Placebo - 40mg bd - for 4 weeks
Placebo: Placebo
|
|---|---|---|
|
Hot Flush Bother
|
2.92 score on a scale
Interval 2.61 to 3.27
|
5.56 score on a scale
Interval 4.96 to 6.27
|
SECONDARY outcome
Timeframe: Daily at bedtime for 14 weeksScore on a scale Menopause Specific Quality of Life (MENQOL) questionnaire 0=not bothered at all - 6=extremely bothered. 4 domains, mean calculated for set of questions in each domain. Overall score is a mean of the means. Highr scor = higher interference.
Outcome measures
| Measure |
Active Drug
n=28 Participants
NK3R antagonist - AZD4901 - 40mg bd - for 4 weeks
NK3R antagonist - AZD4901: Neurokinin 3 receptor antagonist
|
Placebo
n=28 Participants
Placebo - 40mg bd - for 4 weeks
Placebo: Placebo
|
|---|---|---|
|
Hot Flush Interference
|
7.94 Score by participant on 'interference sc
Interval 5.76 to 10.95
|
26.48 Score by participant on 'interference sc
Interval 20.02 to 35.03
|
SECONDARY outcome
Timeframe: Once per week for 48 hours over 14 weeksMean number of flushes detected during the 48 hours by the skin conductance monitoring will be compared each week when the patients receive AZD4901 versus placebo
Outcome measures
| Measure |
Active Drug
n=28 Participants
NK3R antagonist - AZD4901 - 40mg bd - for 4 weeks
NK3R antagonist - AZD4901: Neurokinin 3 receptor antagonist
|
Placebo
n=28 Participants
Placebo - 40mg bd - for 4 weeks
Placebo: Placebo
|
|---|---|---|
|
Skin Conductance Monitor Data.
|
16.22 Number of hot flushes detected by monito
Interval 13.99 to 18.8
|
26.91 Number of hot flushes detected by monito
Interval 23.16 to 31.27
|
Adverse Events
Active Drug First Then Placebo
Placebo First Then Active Drug
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Active Drug First Then Placebo
n=28 participants at risk
2 week baseline period First NK3R antagonist - AZD4901 - 40mg orally bd - for 4 weeks intervention then 2 weeks washout period then second intervention with Matched placebo orally bd for 4 weeks with 2 weeks monitoring period
|
Placebo First Then Active Drug
n=28 participants at risk
2 week baseline period First intervention is Placebo - 40mg bd - for 4 weeks, then 2 weeks washout period, then second intervention with NK3R antagonist - AZD4901 - 40mg orally bd - for 4 weeks with 2 weeks monitoring period
|
|---|---|---|
|
Hepatobiliary disorders
transaminase elevations by treatment and CTCAE grade
|
10.7%
3/28 • Number of events 3 • 10 weeks
|
0.00%
0/28 • 10 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place