Staccato Loxapine Single Dose PK

• Sponsor: Alexza Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00444028
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arms: 5
• Duration (Months): 2
• Patients Per Site Per Month: 24.9

Study Details

Study Description

Brief Summary

The objective of this study was to assess the safety, tolerability and pharmacokinetics of a single inhaled dose of (administered in 1 or 2 puffs) Staccato Loxapine in healthy volunteers.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: inhaled Loxapine 0.625 mg; Drug: inhaled Loxapine 1.25 mg; Drug: inhaled Loxapine 2.5 mg; Drug: inhaled Loxapine 5 mg; Drug: inhaled Loxapine 10 mg; Drug: inhaled Placebo (0 mg)	Phase 1

Detailed Description

Safety and pharmacokinetic data obtained from 50 subjects (between the ages of 18 to 55 years) entered into this randomized, placebo-controlled study. To obtain 50 enrolled subjects, screening procedures and inclusion/exclusion criteria were evaluated for 126 subjects during a variable screening period of up to 21 days. Once enrolled, subjects were randomized to either Staccato Loxapine or Staccato placebo.

Plasma samples for pharmacokinetic analysis were collected beginning on Day 0, pre-dose and continuing for 24 hr post dose. Blood samples for the PK analysis of loxapine and its metabolites (8-OH loxapine, 7-OH loxapine and amoxapine) were obtained at time 0 (immediately before dosing), at 30 sec, 1, 2, 3, 5, 10, 30, 45 min, 1, 2, 4, 6, 12, 24 hr after dosing. Plasma concentrations of loxapine and metabolites were used to estimate the following PK parameters for loxapine and its metabolites: area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf), AUC from time 0 to time tlast, the last quantifiable concentration (AUClast), maximum observed plasma concentration (Cmax), observed time of Cmax (tmax), terminal phase elimination rate constant (ke), apparent terminal elimination half life calculated from ke (T½ ), apparent total body clearance / fraction absorbed calculated from AUCinf and dose (CL/F) (for loxapine and the metabolites where permitted by measurable concentrations).

Safety was evaluated by the incidence of adverse events, clinical laboratory testing (blood chemistry, hematology, and urinalysis), physical examination, vital signs, pulse oximetry, postural vital signs, 12-lead electrocardiogram, pulmonary function tests, continuous 12-lead Holter monitoring, sedation assessments, akathisia assessments.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Safety, Tolerability, and Pharmacokinetics of a Single Dose of Staccato™ Loxapine for Inhalation in Normal, Healthy Volunteers
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Nov 1, 2005
• Actual Study Completion Date: Nov 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Inhaled Loxapine 0.625 mg or Placebo Single 0.625 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine	Drug: inhaled Loxapine 0.625 mg; Single 0.625 mg (lowest) dose of inhaled loxapine; Other Names: ADASUVE ; Drug: inhaled Placebo (0 mg); Single placebo dose of inhaled loxapine; Other Names: PLACEBO
Experimental: Cohort B: Inhaled Loxapine 1.25 mg or Placebo Single 1.25 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine	Drug: inhaled Loxapine 1.25 mg; Single 1.25 mg (2nd) dose of inhaled loxapine; Other Names: ADASUVE ; Drug: inhaled Placebo (0 mg); Single placebo dose of inhaled loxapine; Other Names: PLACEBO
Experimental: Cohort C: Inhaled Loxapine 2.5 mg or Placebo Single 2.5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine	Drug: inhaled Loxapine 2.5 mg; Single 2.5 mg (3rd) dose of inhaled loxapine; Other Names: ADASUVE ; Drug: inhaled Placebo (0 mg); Single placebo dose of inhaled loxapine; Other Names: PLACEBO
Experimental: Cohort D: Inhaled Loxapine 5 mg or Placebo Single 5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine	Drug: inhaled Loxapine 5 mg; Single 5 mg (4th) dose of inhaled loxapine; Other Names: ADASUVE ; Drug: inhaled Placebo (0 mg); Single placebo dose of inhaled loxapine; Other Names: PLACEBO
Experimental: Cohort E: Inhaled Loxapine 10 mg or Placebo Single 10 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine	Drug: inhaled Loxapine 10 mg; Single 10 mg (5th) dose of inhaled loxapine; Other Names: ADASUVE ; Drug: inhaled Placebo (0 mg); Single placebo dose of inhaled loxapine; Other Names: PLACEBO

Outcome Measures

Primary Outcome Measures

1. Tmax [predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours]

   Tmax = time from inhalation to to maximum observed loxapine concentration

2. Half-life [predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours]

   Half-life of the terminal elimination phase of loxapine concentrations

3. ke [predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours]

   elimination rate constant

4. Clearance [predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours]

   clearance (CL/F) of lozxapine

5. Cmax [predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours]

   maximum concentration of loxapine observed

6. Dose Proportionality (AUCinf) by Power Analysis [predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours]

   Dose proportionality by power analysis examines the linear regression of the log-AUC versus log-Dose on a by-patient basis across all doses administered. The slope and 90% confidence interval (CI) provide a clear, quantitative (best practices) assessment of the relationship of drug delivered to dose administered. The units on such analyses are generally those of slope (rise over run), with 1.000 being "perfect". Although any positive slope might be considered clinically useful, a 90% CI within the criteria of 0.800-1.250 may be considered a delivery system which is "as good as it gets".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male and female subjects between the ages of 18 to 55 years, inclusive.

2. Subjects with a body mass index (BMI) ≥21 and ≤30.

3. Subjects who speak, read, and understand English and are willing and able to provide written informed consent on an IRB-approved form prior to the initiation of any study procedures.

4. Subjects who are willing and able to be confined to the Clinical Research Unit (CRU) for approximately 2 days and comply with the study schedule and study requirements.

5. Subjects who are in good general health as determined by a complete medical history, physical examination, 12-lead ECG, spirometry, blood chemistry profile, hematology, and urinalysis.

Exclusion Criteria:

1. Subjects who regularly consume large amounts of xanthine-containing substances (i.e., more than 5 cups of coffee or equivalent amounts of xanthine-containing substances per day).

2. Subjects who have taken prescription or nonprescription medication (with the exception of vitamins and acetaminophen if medically necessary) within 5 days of Visit 2 (Baseline).

3. Subjects who have had an acute illness within 5 days of Visit 2 (Baseline).

4. Subjects who have received an investigational drug within 30 days (or within 5 half lives of the investigational drug, if >30 days) prior to Visit 2 (Baseline).

5. Subjects who have smoked tobacco within the last year.

6. Subjects who have a history within the past 2 years of drug or alcohol dependence or abuse as defined by DSM-4.

7. Subjects with a history of HIV positivity.

8. Subjects with a history of allergy or intolerance to dibenzoxazepines (amoxapine and loxapine).

9. Subjects with a known history of contraindications to anticholinergics (bowel obstructions, urinary retention, acute glaucoma).

10. Subjects with a history of pheochromocytoma, seizure disorder, Parkinson's disease, or Restless Leg Syndrome (RLS).

11. Subjects who test positive for alcohol or have a positive urine drug screen at Visit 1 or Visit 2.

12. Subjects who have hypotension (systolic blood pressure ≤90 mmHg, diastolic blood pressure ≤50 mmHg), or hypertension (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg).

13. Subjects who have a clinically significant ECG abnormality.

14. Subjects with a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure (CHF), stroke, transient ischemic attack (TIA), or a neurological disorder.

15. Subjects who have a history of pulmonary disease that precludes administration of Staccato Loxapine (asthma, bronchitis, bronchospasm, emphysema).

16. Subjects who have an FEV1 less than 80% of predicted values on spirometry assessments at Visit 1.

17. Female subjects who are breastfeeding or have a positive pregnancy test at Visit 1 or Visit 2.

18. Female participants of child-bearing potential or within 1 year of menopause, and sexually active are excluded unless they use a medically acceptable and effective birth control method throughout the study and for 1 week following the end of the study. Medically acceptable methods of contraception include abstinence, diaphragm with spermicide, intrauterine device (IUD), condom with foam or spermicide, vaginal spermicidal suppository, surgical sterilization, and birth control pills. Unacceptable methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.

19. Subjects who have any other disease or condition, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Unit Inc., d/b/a Covance GFI Research	Evansville	Indiana	United States	47714

Sponsors and Collaborators

• Alexza Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Randall Stoltz, MD, West Pharmaceutical Services, GFI Research Center, Evansville, IN 47714

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexza Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00444028
• Other Study ID Numbers: AMDC-004-101
• First Posted: Mar 7, 2007
• Last Update Posted: Nov 20, 2018
• Last Verified: Mar 1, 2007

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexza Pharmaceuticals, Inc.: Schizophrenia, Staccato Loxapine
• Additional relevant MeSH terms: Schizophrenia; Loxapine

Study Results

Participant Flow

Recruitment Details	Fifty subjects were recruited by and studied in the clinical researech unit (CRU). Study dates: 30 September 2005 through 22 November 2005
Pre-assignment Detail	To obtain 50 enrolled subjects, screening procedures and inclusion/exclusion criteria were evaluated for 126 subjects during a variable screening period of up to 21 days. No enrolled participants were excluded from the trial.

Arm/Group Title	Placebo	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg
Arm/Group Description	Staccato placebo inhalation device(s)	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices
Period Title: Overall Study
STARTED	14	7	8	6	7	8
COMPLETED	14	7	8	6	7	8
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg	Total
Arm/Group Description	Staccato placebo inhalation device(s)	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices	Total of all reporting groups
Overall Participants	14	7	8	6	7	8	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	14 100%	7 100%	8 100%	6 100%	7 100%	8 100%	50 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.8 (10.55)	33.4 (10.44)	28 (7.11)	28.2 (6.05)	30.1 (13.53)	27.4 (7.65)	31.7 (10.14)
Sex: Female, Male (Count of Participants)
Female	8 57.1%	3 42.9%	4 50%	4 66.7%	5 71.4%	3 37.5%	27 54%
Male	6 42.9%	4 57.1%	4 50%	2 33.3%	2 28.6%	5 62.5%	23 46%
Region of Enrollment (Count of Participants)
United States	14 100%	7 100%	8 100%	6 100%	7 100%	8 100%	50 100%

Outcome Measures

1. Primary Outcome

Title	Tmax
Description	Tmax = time from inhalation to to maximum observed loxapine concentration
Time Frame	predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

Outcome Measure Data

Analysis Population Description

PK Population (N=36) All subjects exposed to inhaled loxapine who provided concentration data

Arm/Group Title	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg
Arm/Group Description	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices
Measure Participants	7	8	6	7	8
Mean (Standard Deviation) [minutes]	12.6 (21.3)	2.15 (1.31)	2.87 (3.62)	2.13 (0.687)	5.25 (10)

2. Primary Outcome

Title	Half-life
Description	Half-life of the terminal elimination phase of loxapine concentrations
Time Frame	predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

Outcome Measure Data

Analysis Population Description

PK Population (N=36) All subjects exposed to inhaled loxapine who provided concentration data

Arm/Group Title	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg
Arm/Group Description	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices
Measure Participants	7	8	6	7	8
Mean (Standard Deviation) [hours]	5.2 (1.3)	6.56 (1.44)	6.92 (1.94)	6.2 (1.14)	6.14 (2.16)

3. Primary Outcome

Title	ke
Description	elimination rate constant
Time Frame	predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

Outcome Measure Data

Analysis Population Description

PK Population (N=36) All subjects exposed to inhaled loxapine who provided concentration data

Arm/Group Title	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg
Arm/Group Description	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices
Measure Participants	7	8	6	7	8
Mean (Standard Error) [/hour]	.143 (.047)	.111 (.026)	.108 (.033)	.115 (.020)	.122 (.032)

4. Primary Outcome

Title	Clearance
Description	clearance (CL/F) of lozxapine
Time Frame	predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

Outcome Measure Data

Analysis Population Description

PK Population (N=36) All subjects exposed to inhaled loxapine who provided concentration data

Arm/Group Title	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg
Arm/Group Description	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices
Measure Participants	7	8	6	7	8
Mean (Standard Deviation) [L/hour]	56.2 (14.1)	55.9 (13.7)	61.1 (18.8)	53.8 (9.74)	78 (25.8)

5. Primary Outcome

Title	Cmax
Description	maximum concentration of loxapine observed
Time Frame	predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

Outcome Measure Data

Analysis Population Description

PK Population (N=36) All subjects exposed to inhaled loxapine who provided concentration data

Arm/Group Title	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg
Arm/Group Description	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices
Measure Participants	7	8	6	7	8
Mean (Standard Deviation) [ng/mL]	6.5 (8.79)	9.7 (3.49)	62.9 (63)	105 (80.6)	134 (118.8)

6. Primary Outcome

Title	Dose Proportionality (AUCinf) by Power Analysis
Description	Dose proportionality by power analysis examines the linear regression of the log-AUC versus log-Dose on a by-patient basis across all doses administered. The slope and 90% confidence interval (CI) provide a clear, quantitative (best practices) assessment of the relationship of drug delivered to dose administered. The units on such analyses are generally those of slope (rise over run), with 1.000 being "perfect". Although any positive slope might be considered clinically useful, a 90% CI within the criteria of 0.800-1.250 may be considered a delivery system which is "as good as it gets".
Time Frame	predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

Outcome Measure Data

Analysis Population Description

PK Population (N=36) All subjects exposed to inhaled loxapine who provided concentration data

Arm/Group Title	Staccato Loxapine 0.625 mg	Staccato Loxapine 1.25 mg	Staccato Loxapine 2.5 mg	Staccato Loxapine 5 mg	Staccato Loxapine 10 mg
Arm/Group Description	inhalation of loxapine from a single 0.625 mg device	inhalation of loxapine from a two 0.625 mg devices	inhalation of loxapine from a single 2.5 mg device	inhalation of loxapine from a single 5 mg device	inhalation of loxapine from a two 5 mg devices
Measure Participants	7	8	6	7	8
Mean (Standard Deviation) [hr*mcg/L]	11.9 (3.70)	23.4 (4.87)	44.6 (14.7)	95.5 (16.6)	140.6 (44.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Staccato Loxapine 0.625 mg, Staccato Loxapine 1.25 mg, Staccato Loxapine 2.5 mg, Staccato Loxapine 5 mg, Staccato Loxapine 10 mg
	Comments	Dose proportionality by power analysis examines the linear regression of the log-AUC versus log-Dose on a by-patient basis across all doses administered. The slope and 90% confidence interval (CI) provide a clear, quantitative (best practices) assessment of the relationship of drug delivered to dose administered.
	Type of Statistical Test	Other
	Comments	The units on such analyses are generally those of slope (rise over run), with 1.000 being "perfect". Although any positive slope might be considered clinically useful, a 90% CI within the criteria of 0.800-1.250 may be considered a delivery system which is "as good as it gets".
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.909
	Confidence Interval	(2-Sided) 90%; 0.832 to 0.987
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse Event Reporting Description	Adverse events (AEs) were assessed at 17 pre-specified time points for the 24-hour period after dosing, as well as whenever spontaneously reported by the subjects or study staff
Arm/Group Title	Placebo		Staccato Loxapine 0.625 mg		Staccato Loxapine 1.25 mg		Staccato Loxapine 2.5 mg		Staccato Loxapine 5 mg		Staccato Loxapine 10 mg
Arm/Group Description	Staccato placebo inhalation device(s)		inhalation of loxapine from a single 0.625 mg device		inhalation of loxapine from a two 0.625 mg devices		inhalation of loxapine from a single 2.5 mg device		inhalation of loxapine from a single 5 mg device		inhalation of loxapine from a two 5 mg devices
All Cause Mortality
	Placebo		Staccato Loxapine 0.625 mg		Staccato Loxapine 1.25 mg		Staccato Loxapine 2.5 mg		Staccato Loxapine 5 mg		Staccato Loxapine 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/7 (0%)		0/8 (0%)		0/6 (0%)		0/7 (0%)		0/8 (0%)
Serious Adverse Events
	Placebo		Staccato Loxapine 0.625 mg		Staccato Loxapine 1.25 mg		Staccato Loxapine 2.5 mg		Staccato Loxapine 5 mg		Staccato Loxapine 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/7 (0%)		0/8 (0%)		0/6 (0%)		0/7 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Staccato Loxapine 0.625 mg		Staccato Loxapine 1.25 mg		Staccato Loxapine 2.5 mg		Staccato Loxapine 5 mg		Staccato Loxapine 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/14 (42.9%)		4/7 (57.1%)		5/8 (62.5%)		3/6 (50%)		5/7 (71.4%)		8/8 (100%)
Gastrointestinal disorders
Dysgeusia	0/14 (0%)		1/7 (14.3%)		2/8 (25%)		2/6 (33.3%)		2/7 (28.6%)		6/8 (75%)
Nausea	0/14 (0%)		1/7 (14.3%)		1/8 (12.5%)		3/6 (50%)		1/7 (14.3%)		1/8 (12.5%)
General disorders
Fatigue	1/14 (7.1%)		0/7 (0%)		1/8 (12.5%)		1/6 (16.7%)		3/7 (42.9%)		3/8 (37.5%)
Pallor	0/14 (0%)		0/7 (0%)		0/8 (0%)		0/6 (0%)		0/7 (0%)		3/8 (37.5%)
Nervous system disorders
Disturbance in Attention	1/14 (7.1%)		1/7 (14.3%)		1/8 (12.5%)		0/6 (0%)		0/7 (0%)		0/8 (0%)
Dizziness	5/14 (35.7%)		2/7 (28.6%)		2/8 (25%)		3/6 (50%)		4/7 (57.1%)		6/8 (75%)
Headache	2/14 (14.3%)		0/7 (0%)		2/8 (25%)		0/6 (0%)		1/7 (14.3%)		0/8 (0%)
Somnolence	3/14 (21.4%)		1/7 (14.3%)		2/8 (25%)		0/6 (0%)		2/7 (28.6%)		6/8 (75%)

Limitations/Caveats

Absolute bioavailability was not determined because loxapine for intravenous comparator was not available comercially in the US

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.