Trial Outcomes & Findings for Thorough QT Study of Intravenous Amisulpride (NCT NCT02661594)
NCT ID: NCT02661594
Last Updated: 2018-11-29
Results Overview
Maximal mean placebo-corrected change from baseline of QTcF (QT interval corrected for heart rate using the Fridericia formula) for single 5 mg and 40 mg iv doses of APD421. At each time point (2 mins, 8 mins, etc) the QTcF is compared to the pre-dosing "baseline" value, in order to calculate the change in QTcF (ΔQTcF). The value of ΔQTcF at each time point is then compared against the same time point for a placebo infusion, and the difference is calculated (ΔΔQTcF).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
24 hours
Results posted on
2018-11-29
Participant Flow
Forty (40) healthy, non-elderly, Caucasian and Japanese, male or female subjects were planned to enter the study. At least 10 subjects were to be Japanese and at least 40% of subjects for both races were to be male.
Forty (40) healthy subjects entered the study. One subject voluntarily withdrew after Period 1 (moxifloxacin 400 mg) and another subject was withdrawn due to severe non-compliance with the protocol after receiving APD421 5 mg and 40 mg.
Participant milestones
| Measure |
ABCD
A: APD421 5 mg followed by B: APD421 40 mg; C: Moxifloxacin 400 mg; D: Placebo
|
BDAC
B: APD421 40 mg; D: Placebo. A: APD421 5 mg C: Moxifloxacin 400 mg.
|
CADB
C: Moxifloxacin 400 mg A: APD421 5 mg D: Placebo B: APD421 40 mg
|
DCBA
D: Placebo C: Moxifloxacin 400 mg B: APD421 40 mg A: APD421 5 mg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
11
|
10
|
9
|
|
Overall Study
COMPLETED
|
9
|
11
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
ABCD
A: APD421 5 mg followed by B: APD421 40 mg; C: Moxifloxacin 400 mg; D: Placebo
|
BDAC
B: APD421 40 mg; D: Placebo. A: APD421 5 mg C: Moxifloxacin 400 mg.
|
CADB
C: Moxifloxacin 400 mg A: APD421 5 mg D: Placebo B: APD421 40 mg
|
DCBA
D: Placebo C: Moxifloxacin 400 mg B: APD421 40 mg A: APD421 5 mg
|
|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
1
|
0
|
Baseline Characteristics
Thorough QT Study of Intravenous Amisulpride
Baseline characteristics by cohort
| Measure |
ABCD
n=10 Participants
A: APD421 5 mg followed by B: APD421 40 mg; C: Moxifloxacin 400 mg; D: Placebo.
|
BDAC
n=11 Participants
B: APD421 40 mg; D: Placebo. A: APD421 5 mg C: Moxifloxacin 400 mg.
|
CADB
n=10 Participants
C: Moxifloxacin 400 mg A: APD421 5 mg D: Placebo B: APD421 40 mg
|
DCBA
n=9 Participants
D: Placebo C: Moxifloxacin 400 mg B: APD421 40 mg A: APD421 5 mg
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
27.50 Years
STANDARD_DEVIATION 4.22 • n=93 Participants
|
26.82 Years
STANDARD_DEVIATION 4.24 • n=4 Participants
|
30.20 Years
STANDARD_DEVIATION 8.07 • n=27 Participants
|
27.44 Years
STANDARD_DEVIATION 4.93 • n=483 Participants
|
27.99 Years
STANDARD_DEVIATION 5.36 • n=36 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
17 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
23 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
17 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
23 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: 24 hoursMaximal mean placebo-corrected change from baseline of QTcF (QT interval corrected for heart rate using the Fridericia formula) for single 5 mg and 40 mg iv doses of APD421. At each time point (2 mins, 8 mins, etc) the QTcF is compared to the pre-dosing "baseline" value, in order to calculate the change in QTcF (ΔQTcF). The value of ΔQTcF at each time point is then compared against the same time point for a placebo infusion, and the difference is calculated (ΔΔQTcF).
Outcome measures
| Measure |
5 mg IV APD421
n=39 Participants
Single dose of 5 mg IV APD421 infused over 2 minutes
|
40 mg IV APD421
n=39 Participants
Single dose of 40 mg IV APD421 infused over 2 minutes
|
Placebo
n=38 Participants
IV placebo infused over 8 minutes
|
Oral Moxifloxacin
n=39 Participants
Single 400 mg oral dose of moxifloxacin
|
|---|---|---|---|---|
|
Maximal Mean ΔΔQTcF
|
5.0 milliseconds
Interval 2.8 to 7.1
|
23.4 milliseconds
Interval 21.3 to 25.5
|
0.8 milliseconds
Interval -1.4 to 2.9
|
12.3 milliseconds
Interval 10.1 to 25.5
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Amisulpride 5 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Amisulpride 40 mg
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
Moxifloxacin
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=38 participants at risk
Intravenous placebo: two infusions in parallel, one over 2 minutes, one over 8 minutes
Placebo: Placebo comparator to establish baseline for calculating change in QTcF
|
Amisulpride 5 mg
n=39 participants at risk
Intravenous amisulpride 5 mg: infusion over 2 minutes; Intravenous placebo infused in parallel over 8 minutes
Amisulpride 5 mg: Therapeutic dose of amisulpride
|
Amisulpride 40 mg
n=39 participants at risk
Intravenous amisulpride 40 mg: infusion over 8 minutes;
Intravenous placebo infused in parallel over 2 minutes
Amisulpride 40 mg: Supra-therapeutic dose of amisulpride
|
Moxifloxacin
n=39 participants at risk
Oral moxifloxacin 400 mg tablet administered once (not blinded)
Moxifloxacin: Positive control for assay sensitivity
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Infusion-related reaction
|
5.3%
2/38 • Number of events 2 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
5.1%
2/39 • Number of events 2 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
51.3%
20/39 • Number of events 20 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
|
General disorders
Catheter site pain
|
2.6%
1/38 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
2.6%
1/39 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
7.7%
3/39 • Number of events 3 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
2.6%
1/39 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
|
General disorders
Application site pruritus
|
2.6%
1/38 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
7.7%
3/39 • Number of events 3 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection
|
5.3%
2/38 • Number of events 2 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
2.6%
1/39 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
2.6%
1/39 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
2.6%
1/39 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
|
General disorders
Infusion Site Pain
|
2.6%
1/38 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
17.9%
7/39 • Number of events 8 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
|
Nervous system disorders
Headache
|
5.3%
2/38 • Number of events 2 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
2.6%
1/39 • Number of events 1 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
|
Injury, poisoning and procedural complications
Oropharyngeal Pain
|
0.00%
0/38 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
5.1%
2/39 • Number of events 2 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
|
Cardiac disorders
Palpitations
|
0.00%
0/38 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
5.1%
2/39 • Number of events 2 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
0.00%
0/39 • All AE's are to be reported within a timeframe of 24hours.
All AE encountered during the study will be reported in detail in the source documents and noted in the AE section of the CRF from the date of subject consent, throughout the clinical conduct and up to the follow-up visit. for a period of 24hours
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60