15 mg Mirtazapine Orally Disintegrating Tablets, Non-Fasting

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834197
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 31.4

Study Details

Study Description

Brief Summary

This study will compare the relative bioavailability (rate and extent of absorption) of 15 mg Mirtazapine (Orally Disintegrating) Tablets manufactured by TEVA Pharmaceutical Industries, Ltd.; distributed by TEVA Pharmaceuticals USA with that of 15 mg REMERON SolTab® Orally Disintegrating Tablets manufactured for Organon Inc. by CIMA Labs Inc. following a single oral dose (1 x 15 mg) in healthy adult subjects under non-fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Mirtazapine 15 mg (Orally Disintegrating) Tablets; Drug: REMERON SolTab® 15 mg Orally Disintegrating Tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 15 mg Mirtazapine Orally Disintegrating Tablets Under Non-Fasting Conditions
• Study Start Date: Jul 1, 2003
• Actual Primary Completion Date: Aug 1, 2003
• Actual Study Completion Date: Aug 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Mirtazapine 15 mg (Orally Disintegrating) Tablets; 1 x 15 mg, single-dose non-fasting
Active Comparator: 2	Drug: REMERON SolTab® 15 mg Orally Disintegrating Tablets; 1 x 15 mg, single-dose non-fasting

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) [Blood samples collected over a 120 hour period.]

   Bioequivalence based on Cmax.

2. AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) [Blood samples collected over a 120 hour period.]

   Bioequivalence based on AUC0-t.

3. AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) [Blood samples collected over a 120 hour period.]

   Bioequivalence based on AUC0-inf.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Screening Demographics: All subjects selected for this study will be healthy men or women 18 years of age or older at the time of dosing. The subject's body mass index (BMI) should be less than or equal to 30.

• Screening Procedures: Each subject will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before fill implementation of screening procedures.

• Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature. The physical examination will include, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems.

• The screening clinical laboratory will include:

• Hematology: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count;

• Clinical Chemistry: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase;

• HIV antibody, hepatitis B surface antigen, and hepatitis C antibody screens;

• Urinalysis: by dipstick; full microscopic examination of dipstick positive; and

• Urine Drug Screen: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates and phencyclidine.

• Serum Pregnancy Screen (female subjects only)

• If female and:

• of childbearing potential, is practicing an acceptable barrier method of birth control for the duration of the study as judged by the investigator(s), such as condoms, sponge, foams, jellies, diaphragm, intrauterine device (IUD), or abstinence; or

• is postmenopausal for at least 1 year; or

• is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

Exclusion Criteria:

• Subjects with a recent history of drug or alcohol addiction or abuse.

• Subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators).

• Subjects whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant.

• Subjects demonstrating a positive hepatitis B surface antigen screen, hepatitis C antibody screen, or a reactive HIV antibody screen.

• Subjects demonstrating a positive pregnancy screen.

• Subjects who are currently breastfeeding.

• Subjects with a history of clinically significant allergies including drug allergies.

• Subjects with a history of allergic response(s) to mirtazapine or related drugs.

• Subjects with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators).

• Subjects who currently use of have used tobacco products within 90 days of Period I dosing.

• Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing.

• Subjects who report donating greater than 150 mL of blood within 28 days prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study.

• Subjects who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study.

• Subjects who report receiving any investigational drug within 28 days prior to Period I dosing.

• Subjects who report taking any systemic prescription medication in the 14 days prior to Period I dosing.

• Subjects who report an intolerance of direct venipuncture.

• Subjects who report consuming an abnormal diet during the 28 days prior to Period I dosing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute, Ltd.	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: James D. Carlson, Pharm. D., PRACS Institute, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834197
• Other Study ID Numbers: R03-339
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Mirtazapine

Study Results

Participant Flow

Arm/Group Title	Test (Mirtazapine) First	Reference (Remeron®) First
Arm/Group Description	15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in first period followed by 15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in the second period.	15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in first period followed by 15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Test (Mirtazapine) First	Reference (Remeron®) First	Total
Arm/Group Description	15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in first period followed by 15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in the second period.	15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in first period followed by 15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	16 100%	32 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 37.5%	4 25%	10 31.3%
Male	10 62.5%	12 75%	22 68.8%
Race/Ethnicity, Customized (participants) [Number]
American Indian	0 0%	1 6.3%	1 3.1%
Asian	2 12.5%	0 0%	2 6.3%
Black	0 0%	1 6.3%	1 3.1%
White	14 87.5%	14 87.5%	28 87.5%
Region of Enrollment (participants) [Number]
United States	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Description	Bioequivalence based on Cmax.
Time Frame	Blood samples collected over a 120 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Mirtazapine)	Reference (Remeron®)
Arm/Group Description	15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in either period.	15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in either period.
Measure Participants	32	32
Mean (Standard Deviation) [pg/mL]	26345.06 (6917.71)	25942.77 (5550.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Mirtazapine), Reference (Remeron®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	100.59
	Confidence Interval	() 90%; 95.76 to 105.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

2. Primary Outcome

Title	AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Description	Bioequivalence based on AUC0-t.
Time Frame	Blood samples collected over a 120 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Mirtazapine)	Reference (Remeron®)
Arm/Group Description	15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in either period.	15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in either period.
Measure Participants	32	32
Mean (Standard Deviation) [pg*h/mL]	355137.72 (118663.09)	359429 (112502.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Mirtazapine), Reference (Remeron®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	98.17
	Confidence Interval	() 90%; 94.82 to 101.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

3. Primary Outcome

Title	AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Description	Bioequivalence based on AUC0-inf.
Time Frame	Blood samples collected over a 120 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Mirtazapine)	Reference (Remeron®)
Arm/Group Description	15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in either period.	15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in either period.
Measure Participants	32	32
Mean (Standard Deviation) [pg*h/mL]	380545.78 (121850.49)	385738.84 (118600.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Mirtazapine), Reference (Remeron®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	98.25
	Confidence Interval	() 90%; 95.22 to 101.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Principal Investigator is not permitted to discuss or publish trial results.