Trial Outcomes & Findings for ADASUVE-Lorazepam Drug-Drug Interaction (NCT NCT01877642)
NCT ID: NCT01877642
Last Updated: 2017-12-13
Results Overview
Determine the maximum level of sedation for Lorazepam 1 mg IM + ADASUVE 10 mg based on the 100 mm Visual Analog Scale (VAS) ranging from (0=sleepy to 100=wide awake)
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
22 participants
Primary outcome timeframe
24 hours
Results posted on
2017-12-13
Participant Flow
Participant milestones
| Measure |
Open Label (Lorazepam 1 mg + Inhaled Loxapine 10 mg)
Inhaled Staccato loxapine 10 mg + IM lorazepam 1 mg
Lorazepam 1 mg IM: Lorazepam 1 mg intramuscular
Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg
|
Treatment Sequence ABC
Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg
|
Treatment Sequence ACB
Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg
|
Treatment Sequence BCA
Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg
|
Treatment Sequence BAC
Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg
|
Treatment Sequence CAB
Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg
|
Treatment Sequence CBA
Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Overall Study
COMPLETED
|
4
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
ADASUVE-Lorazepam Drug-Drug Interaction
Baseline characteristics by cohort
| Measure |
Open Label Subjects
n=4 Participants
Open label portion of study
|
All Crossover Subjects
n=18 Participants
All 6 crossover treatment sequences
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
32.5 years
STANDARD_DEVIATION 9.68 • n=5 Participants
|
30.4 years
STANDARD_DEVIATION 9.46 • n=7 Participants
|
30.8 years
STANDARD_DEVIATION 9.30 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
18 participants
n=7 Participants
|
22 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: Open label population
Determine the maximum level of sedation for Lorazepam 1 mg IM + ADASUVE 10 mg based on the 100 mm Visual Analog Scale (VAS) ranging from (0=sleepy to 100=wide awake)
Outcome measures
| Measure |
Open Label Group
n=4 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Maximum Level of Sedation for Lorazepam 1 mg IM + ADASUVE 10 mg
|
12.3 units on a scale
Standard Deviation 6.65
|
—
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: Pharmacodynamics Population
LS Mean ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for respiration rate following administration of Lorazepam+Loxapine compared to the same measure following each control drug given alone (Lorazepam, Loxapine)
Outcome measures
| Measure |
Open Label Group
n=18 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
n=18 Participants
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Relative Pharmacodynamic Effect on Respiration Rate for Combined vs Individual (Lorazepam, Loxapine)
|
94.3 percentage of effect on control drug
Interval 91.5 to 97.3
|
97.3 percentage of effect on control drug
Interval 94.3 to 100.0
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Pharmacodynamics Population
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for systolic blood pressure following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Outcome measures
| Measure |
Open Label Group
n=18 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
n=18 Participants
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Relative Pharmacodynamic Effect on Systolic Blood Pressure for Combined vs Individual (Lorazepam, Loxapine)
|
100 percentage of effect on control drug
Interval 97.8 to 103.0
|
102 percentage of effect on control drug
Interval 97.8 to 105.0
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Pharmacodynamics Population
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for sedation based on a 100 mm Visual Analog Scale (VAS) ranging from (0=sleepy to 100=wide awake) following administration of Lorazepam+Loxapine compared to the same measure following each control drug given alone (Lorazepam, Loxapine)
Outcome measures
| Measure |
Open Label Group
n=18 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
n=18 Participants
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Relative Pharmacodynamic Effect on Sedation for Combined vs Individual (Lorazepam, Loxapine)
|
41.7 percentage of effect on control drug
Interval 33.8 to 51.5
|
95.7 percentage of effect on control drug
Interval 77.6 to 118.0
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Pharmacodynamic population
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for pulse oximetry following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Outcome measures
| Measure |
Open Label Group
n=18 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
n=18 Participants
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Relative Pharmacodynamic Effect on Pulse Oximetry for Combined vs Individual (Lorazepam, Loxapine)
|
99.7 percentage of effect on control drug
Interval 99.4 to 100.1
|
100.3 percentage of effect on control drug
Interval 100.0 to 100.6
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Pharmacodynamic population
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for heart rate following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Outcome measures
| Measure |
Open Label Group
n=18 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
n=18 Participants
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Relative Pharmacodynamic Effect on Heart Rate for Combined vs Individual (Lorazepam, Loxapine)
|
96.9 percentage of effect on control drug
Interval 91.4 to 102.7
|
99.7 percentage of effect on control drug
Interval 94.0 to 105.7
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Pharmacodynamic population
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for diastolic blood pressure following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Outcome measures
| Measure |
Open Label Group
n=18 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
n=18 Participants
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Relative Pharmacodynamic Effect on Diastolic Blood Pressure for Combined vs Individual (Lorazepam, Loxapine)
|
101.8 percentage of effect on control drug
Interval 98.0 to 105.7
|
100.3 percentage of effect on control drug
Interval 96.6 to 104.2
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Pharmacodynamic population
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for Cogscreen Pathfinder Response following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Outcome measures
| Measure |
Open Label Group
n=18 Participants
Lorazepam 1 mg IM + Inhaled loxapine 10 mg
|
Lorazepam+Loxapine / Loxapine
n=18 Participants
Lorazepam 1 mg IM + Inhaled Staccato Loxapine 10 mg compared to Inhaled Loxapine 10 mg
|
|---|---|---|
|
Relative Pharmacodynamic Effect on Cogscreen Pathfinder Response for Combined vs Individual (Lorazepam, Loxapine)
|
134 percentage of effect on control drug
Interval 122.0 to 147.0
|
133 percentage of effect on control drug
Interval 121.0 to 146.0
|
Adverse Events
Open Label (Lorazepam 1 mg + Inhaled Loxapine 10 mg)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Lorazepam 1 mg IM
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Lorazepam 1 mg IM + Inhaled Loxapine 10 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Inhaled Loxapine 10 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Open Label (Lorazepam 1 mg + Inhaled Loxapine 10 mg)
n=4 participants at risk
Inhaled Staccato loxapine 10 mg + IM lorazepam 1 mg
Lorazepam 1 mg IM: Lorazepam 1 mg intramuscular
Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg
|
Lorazepam 1 mg IM
n=18 participants at risk
Lorazepam 1 mg IM + Inhaled placebo
Lorazepam 1 mg IM: Lorazepam 1 mg intramuscular
Inhaled Placebo: Inhaler with no drug in it to mimic the ADASUVE inhaler
|
Lorazepam 1 mg IM + Inhaled Loxapine 10 mg
n=18 participants at risk
Lorazepam 1 mg IM + Inhaled Staccato loxapine 10 mg
Lorazepam 1 mg IM: Lorazepam 1 mg intramuscular
Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg
|
Inhaled Loxapine 10 mg
n=18 participants at risk
Inhaled Staccato loxapine 10 mg + IM placebo
Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg
Placebo IM: intramuscular placebo to mimic lorazepam 1 mg IM
|
|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
25.0%
1/4 • Number of events 1 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/4 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
5.6%
1/18 • Number of events 1 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
|
Nervous system disorders
Headache
|
0.00%
0/4 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
5.6%
1/18 • Number of events 1 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
25.0%
1/4 • Number of events 1 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
0.00%
0/18 • From time of first study treatment to 30 days after the last study treatment
Adverse events reported to the investigator by telephone report, by historical report at the follow-up visit, or to study personnel during the follow-up assessment, regardless of treatment group (if known) or suspected causal relationship to study drug, were recorded on the AE CRF. AEs were collected pre-dose, 15, 30, 45, 60, 75, 90 \& 105 min; 2, 3, 4, 5, 6, 7, 8, 9 12 and 24 hours.
|
Additional Information
Executive VP, Research & Development, Regulatory & Quality
Alexza Pharmaceuticals, Inc
Phone: 650.944.7777
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60