A Trial to Determine Whether Two Differing Strength Tablets (3 x 5 mg Versus 1 x 15 mg) of Sublingually Org 5222 (Asenapine) Are Safe and Equal in Subjects With Schizophrenia or Schizoaffective Disorder (P05937)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01101464
• Collaborator: (none)
• Enrollment: 8
• Arms: 2
• Duration (Months): 2

Study Details

Study Description

Brief Summary

A trial to compare if one 15 mg under the tongue tablet is equal to three 5 mg under the tongue tablets of Org 5222 (asenapine) in subjects with schizophrenia or schizoaffective disorder delivered.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder	Drug: Asenapine 3x5mg followed by 1x15mg; Drug: Asenapine 1x15mg followed by 3x5mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Single-center, Open-label, 2-way Crossover Relative Bioavailability and Safety Trial With Two Differing Strength Tablets (3 x 5 mg vs. 1 x 15 mg) of Sublingually Administered Org 5222 in Subjects With Schizophrenia or Schizoaffective Disorder.
• Study Start Date: Oct 1, 2002
• Actual Primary Completion Date: Dec 1, 2002
• Actual Study Completion Date: Dec 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Asenapine Sequence 1	Drug: Asenapine 3x5mg followed by 1x15mg; Three 5 mg sublingual tablets (15 mg) given twice daily for 2 days followed by one 15 mg sublingual tablet given twice daily for 1.5 days; Other Names: Org 5222, SCH 900274
Experimental: Asenapine Sequence 2	Drug: Asenapine 1x15mg followed by 3x5mg; One 15 mg sublingual tablet given twice daily for 2 days followed by three 5 mg sublingual tablets (15 mg) given twice daily for 1.5 days.

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic Parameter of Maximum Plasma Concentration (Cmax) of Two Differing Tablet Strengths (3 x 5 mg and 1 x 15 mg) of Sublingually Administered Org 5222 (Asenapine) [Day 5 & Day 7]

   The primary objective is to compare the bioavailability using pharmacokinetic parameter of maximum plasma concentration (Cmax) of two differing tablet strengths (3 x 5 mg and 1 x 15 mg) of sublingually administered Org 5222 Measurements were performed after each cross-over period: Day 5 measurement for 3x5mg for participants from Sequence 1 and 1x15mg for participants from Sequence 2; Day 7 measurement for 1x15mg for participants from Sequence 1 and 3x5mg for participants from Sequence 2.

2. Pharmacokinetic Parameter of Time of Occurrence of Cmax (Tmax) of Two Differing Tablet Strengths (3 x 5 mg and 1 x 15 mg) of Sublingually Administered Org 5222 (Asenapine) [Day 5 & Day 7]

   The primary objective is to compare the bioavailability using pharmacokinetic parameter of time of occurrence of Cmax (Tmax) of two differing tablet strengths (3 x 5 mg and 1 x 15 mg) of sublingually administered Org 5222. Measurements were performed after each cross-over period: Day 5 measurement for 3x5mg for participants from Sequence 1 and 1x15mg for participants from Sequence 2; Day 7 measurement for 1x15mg for participants from Sequence 1 and 3x5mg for participants from Sequence 2

3. Pharmacokinetic Parameter of Area Under the Curve (AUC) of Two Differing Tablet Strengths (3 x 5 mg and 1 x 15 mg) of Sublingually Administered Org 5222 (Asenapine) [Day 5 & Day 7]

   The primary objective is to compare the bioavailability using pharmacokinetic parameter of area under the curve (AUC) of two differing tablet strengths (3 x 5 mg and 1 x 15 mg) of sublingually administered Org 5222. Measurements were performed after each cross-over period: Day 5 measurement for 3x5mg for participants from Sequence 1 and 1x15mg for participants from Sequence 2; Day 7 measurement for 1x15mg for participants from Sequence 1 and 3x5mg for participants from Sequence 2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• must provide written informed consent after the scope and nature of the investigation has been explained to them, but before signing any trial-related activities, including screening evaluations;

• must be at least 18 and less than 65 years of age;

• can be either male or female; females must be either surgically sterile, postmenopausal for at least 1 year, or non-pregnant using a method of birth control that was acceptable to the investigator;

• must be able to speak, read and understand English and be able to respond to questions and follow simple instructions;

• must be diagnosed at the screening interview according to Diagnostic & Statistical Manual of Mental Disorders, 4th edition (DSM-IV), with non-first episode schizophrenia or schizoaffective disorder (295.70); if schizophrenia, must be of the following types: schizophrenia of the paranoid type (295.30), schizophrenia of the disorganized type (295.10), schizophrenia of the catatonic type (295.20), schizophrenia of the undifferentiated type (295.90), schizophrenia of the residual type (295.60);

• must have discontinued all use of all antipsychotic medication except depot neuroleptics at least 3 days prior to baseline. For depot neuroleptics, subjects must have completed 1 dosing interval by the baseline interview;

• must not have taken any experimental medication for at least 30 days prior to baseline;

• with hypothyroidism, diabetes, high blood pressure, or chronic respiratory conditions can be considered as candidates for enrollment in the trial if their conditions are stable, they are receiving standard therapies for the condition, the prescribed dose and regimen of medication is stable for at least 3 months, and all appropriate clinical and laboratory parameters are within the clinically acceptable limits for the condition, and

• must be willing to remain in the hospital a minimum of 14 days to approximately 17 days (minimum of a 3- to a maximum of a 7-day washout period, a minimum of an 8-day in-patient period, and a possible 3-day stabilization period, if needed, prior to discharge).

Exclusion Criteria:

• they have any untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic, or cerebrovascular disease, or malignancy;

• they are considered obese by the investigator (e.g., greater than 30% above ideal body weight);

• they have a seizure disorder or are taking anticonvulsants to prevent seizures;

• they have any clinically relevant electrocardiogram (ECG) abnormalities at the screening visit (Day -2) or at baseline (Day 0);

• they have a history of a clinically significant cardiac event that required resuscitation;

• at the screening visit, on admission to the trial, during the washout period or at baseline (Day 0), they have any clinically significant abnormal laboratory, vital sign, or physical examination findings which, in the opinion of the investigator, would preclude trial participation;

• they require concomitant treatment with hypnotics (for sleep induction) other than chloral hydrate ≤3000 mg/day, or Ambien (zolpidem tartrate) ≤10 mg qhs, and (for agitation) a benzodiazepine such as lorazepam, ≤10 mg/day;

• they have a score greater than mild at baseline (score >2) on any item of the Abnormal Involuntary Movement Scale (AIMS) assessment at screening and/or require ongoing treatment with anticholinergic medication beyond baseline (Day 0);

• they have a history of significant drug and/or alcohol abuse (according to DSM-IV criteria 305.00) within 30 days before the screening visit;

• they have a confirmed positive result on the alcohol/drug screen test for alcohol, illegal (excluding marijuana), or non-prescribed drugs at screening or at hospital admission;

• they had a primary psychiatric diagnosis (according to DSM-IV criteria) other than schizophrenia or schizoaffective disorder;

• they are actively suicidal at the screening visit, or become so at admission to the hospital, during the washout period, or at baseline (Day 0);

• they have a Clinical Global Impression (CGI) (Severity of Illness) rating greater than moderately ill (score >4) at screening or baseline;

• they are non-compliant (>25%) during the washout period (including baseline Day 0); or,

• they are pregnant, intend to become pregnant during the course of the trial, or are currently nursing mothers during the course of the trial.

• require concomitant medications that are substrates, inhibitors, or inducers of Cytochrome P450 CYP3A4.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01101464
• Other Study ID Numbers: P05937
• First Posted: Apr 12, 2010
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders; Asenapine

Study Results

Participant Flow

Pre-assignment Detail	All subjects rec'd asenapine 5mg BID on Day 1 & 10mg BID on Day 2. Subjects rec'd 15mg BID (either 3x5mg or 1x15mg according to their randomized sequence) from the morning dose on Day 3 through the morning dose on Day 5, followed by the alternate treatment (either 3x5mg or 1x15mg) from the evening dose on Day 5 through the morning dose on Day 7.

Arm/Group Title	Asenapine, (3) 5mg Then (1) 15 mg	Asenapine, (1) 15 mg Then (3) 5 mg
Arm/Group Description	Three 5 mg sublingual tablets (15 mg) given twice daily for 2 days followed by one 15 mg sublingual tablet given twice daily for 1.5 days.	One 15 mg sublingual tablet given twice daily for 2 days followed by three 5 mg sublingual tablets (15 mg) given twice daily for 1.5 days.
Period Title: Day 1 Through AM Dose of Day 5
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0
Period Title: Day 1 Through AM Dose of Day 5
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Asenapine, (3) 5 mg Then (1) 15 mg	Asenapine, (1) 15 mg Then (3) 5 mg	Total
Arm/Group Description	Three 5 mg sublingual tablets (15 mg) given twice daily for 2 days followed by one 15 mg sublingual tablet given twice daily for 1.5 days	One 15 mg sublingual tablet given twice daily for 2 days followed by three 5 mg sublingual tablets (15 mg) given twice daily for 1.5 days	Total of all reporting groups
Overall Participants	4	4	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	4 100%	8 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 25%	1 25%	2 25%
Male	3 75%	3 75%	6 75%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Parameter of Maximum Plasma Concentration (Cmax) of Two Differing Tablet Strengths (3 x 5 mg and 1 x 15 mg) of Sublingually Administered Org 5222 (Asenapine)
Description	The primary objective is to compare the bioavailability using pharmacokinetic parameter of maximum plasma concentration (Cmax) of two differing tablet strengths (3 x 5 mg and 1 x 15 mg) of sublingually administered Org 5222 Measurements were performed after each cross-over period: Day 5 measurement for 3x5mg for participants from Sequence 1 and 1x15mg for participants from Sequence 2; Day 7 measurement for 1x15mg for participants from Sequence 1 and 3x5mg for participants from Sequence 2.
Time Frame	Day 5 & Day 7

Outcome Measure Data

Analysis Population Description

All participants were included in both treatment comparisons (as per cross over design).

Arm/Group Title	Asenapine 3x5mg	Asenapine 1x15mg
Arm/Group Description	Three 5 mg sublingual tablets (15 mg) given twice daily for 2 or 1.5 days (depending on sequence of participant)	One 15 mg sublingual tablet given twice daily for 2 or 1.5 days (depending on sequence of participant)
Measure Participants	8	8
Mean (Standard Deviation) [ng/mL]	6.89 (3.08)	6.38 (2.76)

2. Primary Outcome

Title	Pharmacokinetic Parameter of Time of Occurrence of Cmax (Tmax) of Two Differing Tablet Strengths (3 x 5 mg and 1 x 15 mg) of Sublingually Administered Org 5222 (Asenapine)
Description	The primary objective is to compare the bioavailability using pharmacokinetic parameter of time of occurrence of Cmax (Tmax) of two differing tablet strengths (3 x 5 mg and 1 x 15 mg) of sublingually administered Org 5222. Measurements were performed after each cross-over period: Day 5 measurement for 3x5mg for participants from Sequence 1 and 1x15mg for participants from Sequence 2; Day 7 measurement for 1x15mg for participants from Sequence 1 and 3x5mg for participants from Sequence 2
Time Frame	Day 5 & Day 7

Outcome Measure Data

Analysis Population Description

All participants were included in both treatment comparisons (as per cross over design).

Arm/Group Title	Asenapine 3x5mg	Asenapine 1x15mg
Arm/Group Description	Three 5 mg sublingual tablets (15 mg) given twice daily for 2 or 1.5 days (depending on sequence of participant)	One 15 mg sublingual tablet given twice daily for 2 or 1.5 days (depending on sequence of participant)
Measure Participants	8	8
Mean (Full Range) [Hours]	1.25	1.00

3. Primary Outcome

Title	Pharmacokinetic Parameter of Area Under the Curve (AUC) of Two Differing Tablet Strengths (3 x 5 mg and 1 x 15 mg) of Sublingually Administered Org 5222 (Asenapine)
Description	The primary objective is to compare the bioavailability using pharmacokinetic parameter of area under the curve (AUC) of two differing tablet strengths (3 x 5 mg and 1 x 15 mg) of sublingually administered Org 5222. Measurements were performed after each cross-over period: Day 5 measurement for 3x5mg for participants from Sequence 1 and 1x15mg for participants from Sequence 2; Day 7 measurement for 1x15mg for participants from Sequence 1 and 3x5mg for participants from Sequence 2.
Time Frame	Day 5 & Day 7

Outcome Measure Data

Analysis Population Description

All participants were included in both treatment comparisons (as per cross over design).

Arm/Group Title	Asenapine 3x5mg	Asenapine 1x15mg
Arm/Group Description	Three 5 mg sublingual tablets (15 mg) given twice daily for 2 or 1.5 days (depending on sequence of participant).	One 15 mg sublingual tablet given twice daily for 2 or 1.5 days (depending on sequence of participant).
Measure Participants	8	8
Mean (Standard Deviation) [ng*h/mL]	41.3 (18.2)	41.1 (17.1)

Adverse Events

Adverse Event Reporting Description	All subjects rec'd asenapine 5mg BID on Day 1 & 10mg BID on Day 2. Subjects rec'd 15mg BID (either 3x5mg or 1x15mg according to their randomized sequence) from the morning dose on Day 3 through the morning dose on Day 5, followed by the alternate treatment (either 3x5mg or 1x15mg) from the evening dose on Day 5 through the morning dose on Day 7.
Arm/Group Title	Asenapine, (3) 5 mg Then (1) 15 mg		Asenapine, (1) 15 mg Then (3) 5 mg
Arm/Group Description	Three 5 mg sublingual tablets (15 mg) given twice daily for 2 days followed by one 15 mg sublingual tablet given twice daily for 1.5 days		One 15 mg sublingual tablet given twice daily for 2 days followed by three 5 mg sublingual tablets (15 mg) given twice daily for 1.5 days.
All Cause Mortality
	Asenapine, (3) 5 mg Then (1) 15 mg		Asenapine, (1) 15 mg Then (3) 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Asenapine, (3) 5 mg Then (1) 15 mg		Asenapine, (1) 15 mg Then (3) 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Asenapine, (3) 5 mg Then (1) 15 mg		Asenapine, (1) 15 mg Then (3) 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		3/4 (75%)
Gastrointestinal disorders
Dyspepsia	1/4 (25%)	1	1/4 (25%)	1
Nervous system disorders
Extrapyramidal disosrder	1/4 (25%)	1	1/4 (25%)	1
Psychiatric disorders
Anxiety	1/4 (25%)	1	1/4 (25%)	1
Insomnia	1/4 (25%)	1	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All publications must be based on data validated by Organon. Any such communication will first be submitted to Organon, at least 6 weeks ahead of time for written consent. Organon shall have the right to make its consent conditional upon proper representation of the interpretation of both Organon and the investigator. In any communication concerning this trial, the authors of this protocol will be included in the list of authors.