Trial Outcomes & Findings for Staccato Prochlorperazine Thorough QT/QTc (NCT NCT00543062)
NCT ID: NCT00543062
Last Updated: 2019-03-11
Results Overview
Time-matched differences in QTcI values between the maximum of the mean difference from baseline of the QTcI interval after time-matched placebo subtraction for treatment at 11 post-inhalation times.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
Results posted on
2019-03-11
Participant Flow
Eligible subjects reported to the CRU for baseline assessments (Day 1). The subjects were confined to the Clinical Research Unit under continuous medical or paramedical observation until at least 24 hours after each dose of Staccato Prochlorperazine or placebo.
Participant milestones
| Measure |
Treatment Sequence ABCD
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
Treatment Sequence BDAC
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
Treatment Sequence CABD
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
Treatment Sequence DCBA
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
12
|
12
|
|
Overall Study
COMPLETED
|
10
|
11
|
9
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
3
|
1
|
Reasons for withdrawal
| Measure |
Treatment Sequence ABCD
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
Treatment Sequence BDAC
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
Treatment Sequence CABD
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
Treatment Sequence DCBA
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
2
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
1
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Staccato Prochlorperazine Thorough QT/QTc
Baseline characteristics by cohort
| Measure |
Safety Population
n=48 Participants
All subjects were to receive all 4 treatments in this 4 treatment crossover
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
48 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
35.7 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
48 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hrPopulation: QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between prochlorperazine and placebo exposures per ICH Guideline E14 for a thorough QT/QTc study.
Time-matched differences in QTcI values between the maximum of the mean difference from baseline of the QTcI interval after time-matched placebo subtraction for treatment at 11 post-inhalation times.
Outcome measures
| Measure |
Placebo+Inhaled Prochlorperazine 5 mg Crossover Subjects
n=42 Participants
All subjects who completed both treatments B and C: Treatment: B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Placebo+Inhaled Prochlorperazine 10 mg Crossover Subjects
n=42 Participants
All subjects who completed both treatments A and C: Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, C = Inhaled placebo + oral placebo.
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Inhaled Prochlorperazine 10 mg
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
|---|---|---|---|
|
Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
|
5.493 milliseconds
Interval 2.635 to 8.351
|
5.229 milliseconds
Interval 2.405 to 8.052
|
—
|
SECONDARY outcome
Timeframe: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hrPopulation: 846 paired QTcI and prochlorperazine concentration pairs from 42 subjects receiving prochlorperazine (5 or 10 mg) Each measure was based on the individual (within subject) corrected differences between prochlorperazine and placebo exposures per ICH Guideline E14 for a thorough QT study.
QTcI @ median prochlorperazine concentration (3.75 mcg/mL) based on linear and nonlinear regression of QTcI versus time matched serum prochlorperazine concentrations
Outcome measures
| Measure |
Placebo+Inhaled Prochlorperazine 5 mg Crossover Subjects
n=42 Participants
All subjects who completed both treatments B and C: Treatment: B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Placebo+Inhaled Prochlorperazine 10 mg Crossover Subjects
All subjects who completed both treatments A and C: Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, C = Inhaled placebo + oral placebo.
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Inhaled Prochlorperazine 10 mg
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
|---|---|---|---|
|
QTcI Versus Prochlorperazine Concentration
|
2.83 milliseconds
Interval 1.11 to 4.56
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: QT Population (placebo and prochlorperazine only)
Numbers and Percents of Subjects with QTcI exceeding 450 ms
Outcome measures
| Measure |
Placebo+Inhaled Prochlorperazine 5 mg Crossover Subjects
n=44 Participants
All subjects who completed both treatments B and C: Treatment: B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Placebo+Inhaled Prochlorperazine 10 mg Crossover Subjects
n=44 Participants
All subjects who completed both treatments A and C: Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, C = Inhaled placebo + oral placebo.
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Inhaled Prochlorperazine 10 mg
n=46 Participants
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
|---|---|---|---|
|
Numbers and % of Subjects With QTcI > 450 ms
|
3 Participants
|
4 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hrPopulation: QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between active and placebo exposures per ICH Guideline E14 for a thorough
Numbers and Percents of Subjects with QTcI exceeding 480 ms at any of the outcome measure time points
Outcome measures
| Measure |
Placebo+Inhaled Prochlorperazine 5 mg Crossover Subjects
n=45 Participants
All subjects who completed both treatments B and C: Treatment: B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Placebo+Inhaled Prochlorperazine 10 mg Crossover Subjects
n=45 Participants
All subjects who completed both treatments A and C: Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, C = Inhaled placebo + oral placebo.
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Inhaled Prochlorperazine 10 mg
n=46 Participants
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
|---|---|---|---|
|
Numbers and % of Subjects With QTcI > 480 ms
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hrPopulation: QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between active and placebo exposures per ICH Guideline E14 for a thorough QT/QTc study.
Numbers and Percents of Subjects with QTcI increase from baseline exceeding 30 ms at any of the outcome measure time points
Outcome measures
| Measure |
Placebo+Inhaled Prochlorperazine 5 mg Crossover Subjects
n=43 Participants
All subjects who completed both treatments B and C: Treatment: B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Placebo+Inhaled Prochlorperazine 10 mg Crossover Subjects
n=44 Participants
All subjects who completed both treatments A and C: Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, C = Inhaled placebo + oral placebo.
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Inhaled Prochlorperazine 10 mg
n=46 Participants
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
|---|---|---|---|
|
Numbers and % of Subjects With QTcI Change > 30 ms
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hrPopulation: QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between active and placebo exposures per ICH Guideline E14 for a thorough QT/QTc study.
Numbers and Percents of Subjects with QTcI increase from baseline exceeding 60 ms at any of the outcome measure time points
Outcome measures
| Measure |
Placebo+Inhaled Prochlorperazine 5 mg Crossover Subjects
n=43 Participants
All subjects who completed both treatments B and C: Treatment: B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Placebo+Inhaled Prochlorperazine 10 mg Crossover Subjects
n=44 Participants
All subjects who completed both treatments A and C: Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, C = Inhaled placebo + oral placebo.
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Inhaled Prochlorperazine 10 mg
n=46 Participants
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
|---|---|---|---|
|
Numbers and % of Subjects With QTcI Change > 60 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1, 1.5, 2, 2.5, 3, 5 hoursPopulation: QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between moxifloxacin and placebo exposures per ICH Guideline E14 for a thorough QT study.
A thorough QT/QTc study may be considered to have demonstrated assay sensitivity if 1 or more of the lower 95% CI values exceeds 5 msec
Outcome measures
| Measure |
Placebo+Inhaled Prochlorperazine 5 mg Crossover Subjects
n=42 Participants
All subjects who completed both treatments B and C: Treatment: B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Placebo+Inhaled Prochlorperazine 10 mg Crossover Subjects
All subjects who completed both treatments A and C: Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, C = Inhaled placebo + oral placebo.
The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
|
Inhaled Prochlorperazine 10 mg
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
|---|---|---|---|
|
Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity)
|
9.595 milliseconds
Interval 6.062 to 13.128
|
—
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Inhaled Prochlorperazine 5 mg
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Inhaled Prochlorperazine 10 mg
Serious events: 0 serious events
Other events: 29 other events
Deaths: 0 deaths
Oral Moxifloxacin 400 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=45 participants at risk
Inhaled placebo Oral placebo
Inhaled placebo: Inhaled Staccato placebo (0 mg)
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
|
Inhaled Prochlorperazine 5 mg
n=44 participants at risk
Staccato prochlorperazine 5 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 5 mg: Staccato prochlorperazine 5 mg, single dose
|
Inhaled Prochlorperazine 10 mg
n=46 participants at risk
Staccato prochlorperazine 10 mg, single dose Oral placebo
Oral placebo: Oral placebo (identical to 400 mg moxifloxacin)
Inhaled prochlorperazine 10 mg: Inhaled prochlorperazine 10 mg, single dose
|
Oral Moxifloxacin 400 mg
n=43 participants at risk
Oral moxifloxacin 400 mg Inhaled placebo
Inhaled placebo: Inhaled Staccato placebo (0 mg)
Oral moxifloxacin: Oral moxifloxacin 400 mg, si/ngle dose
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Dysgeusia
|
0.00%
0/45 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
2.3%
1/44 • Number of events 1 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
10.9%
5/46 • Number of events 5 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
0.00%
0/43 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/45 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
4.5%
2/44 • Number of events 2 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
4.3%
2/46 • Number of events 2 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
0.00%
0/43 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
|
Nervous system disorders
Headache
|
4.4%
2/45 • Number of events 2 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
9.1%
4/44 • Number of events 4 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
4.3%
2/46 • Number of events 2 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
4.7%
2/43 • Number of events 2 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
|
Nervous system disorders
Somnolence
|
0.00%
0/45 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
9.1%
4/44 • Number of events 4 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
13.0%
6/46 • Number of events 6 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
0.00%
0/43 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/45 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
2.3%
1/44 • Number of events 1 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
6.5%
3/46 • Number of events 3 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
0.00%
0/43 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.2%
1/45 • Number of events 1 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
29.5%
13/44 • Number of events 13 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
26.1%
12/46 • Number of events 12 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
2.3%
1/43 • Number of events 1 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
|
2.2%
1/45 • Number of events 1 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
15.9%
7/44 • Number of events 7 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
19.6%
9/46 • Number of events 9 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
2.3%
1/43 • Number of events 1 • Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed predose and at 14 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
|
Additional Information
Executive VP, Research & Development, Regulatory & Quality
Alexza Pharmaceuticals, Inc
Phone: 650.944.7071
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60