Sumatriptan Succinate 100 mg Tablets Under Non-Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00846885
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 14

Study Details

Study Description

Brief Summary

The objective of this study is to compare the rate and extent of absorption of sumatriptan from a test formulation of Sumatriptan Succinate 100 mg Tablets versus the reference Imitrex® 100 mg Tablets under fed conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Sumatriptan Succinate; Drug: Imitrex®	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Randomized, Two-Way, Single-Dose, Open-Label Study to Evaluate the Bioequivalence of a Test Tablet Formulation of Sumatriptan Succinate, (100mg), Compared to and Equivalent Dose of a Commercially Available Reference Drug Product (Imitrex®, GlaxoSmithKline, USA) in 28 Fed, Healthy, Adult Subjects.
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Sep 1, 2004
• Actual Study Completion Date: Oct 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Sumatriptan Succinate; 100 mg Tablet
Active Comparator: 2	Drug: Imitrex®; 100 mg Tablet

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) [Blood samples collected over a 12 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 12 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 12 hour period.]

   Bioequivalence based on AUC0-inf.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Non-smoking (i.e. non-smoker or non-tobacco user for at least 90 days prior to pre-study medical screening) male or female within an age range of 18-40 years.

• Body Mass Index (BMI = weight/height2) greater than 19 kg/m2 and less than 26 kg/m2.

• Normal findings in the physical examination, vital signs (blood pressure between 100-140/60-90 mmHg, heart rate between 50-80 beats/min) and 12-lead ECG.

• Negative for drugs of abuse, nicotine, alcohol, hepatitis B-surface antigen, hepatitis C and HIV, and for female subjects, pregnancy (serum β-CG).

• No clinical laboratory values outside of the acceptable range as defined by BCR, unless the Principal Investigator decides they are not clinically significant.

• Female subjects who are surgically sterile for at least six months or post-menopausal for at least one year, or who will avoid pregnancy prior to the study, during the study and up until one month after the end of the study.

Exclusion Criteria

• Known history of hypersensitivity to sumatriptan (e.g. Imitrex®, Imigran®) and/or related drugs such as almotriptan, naratriptan, rizatriptan and zolmitriptan

• Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, hematological, liver or kidney disease, unless judged not clinically significant by the Principal Investigator or medical designate.

• Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.

• Any clinically significant illness during the last four weeks prior to entry into this study.

• Presence of any significant physical or organ abnormality.

• Any subject with a history of drug abuse.

• Any history or evidence of psychiatric or psychological disease (including depression) unless deemed not clinically significant by the Principal Investigator, or medical designate.

• Use of any prescription medication within 14 days preceding entry into this study.

• Use of any monoamine oxidase (MAO) inhibitor drugs such as phenelzine or tranylcypromine within 30 days preceding entry into this study.

• Use of over the counter (OTC) medication within seven days preceding entry into this study (except for spermicidal/barrier contraceptive products).

• Female subjects: use of oral contraceptives or contraceptive implants (such as Norplant®) within 30 days prior to drug administration or a depot injection of progestogen drug (e.g. Depo-Provera®) within one year prior to drug administration.

• Female subjects: presence of pregnancy or lactation.

• Any subject who has had blood drawn within 56 days preceding this study, taken during the conduct of any clinical study at a facility other than BCR, or within the lockout period specified by a previous study conducted at BCR.

• Participation in a clinical trial with an investigational drug within 30 days preceding this study.

• Any subject who has donated blood within 56 days preceding this study.

• Any subject who has participated as a plasma donor in a plasmapheresis program within seven days preceding this study.

• Significant or recent history of asthma (after 12 years of age).

• Any subject with a recent (less than one year) history of alcohol abuse.

• Known history of frequent headaches or migraines.

• Any subject with a parental or sibling history of heart attack or stroke that occurred under the age of 40 years.

• Intolerance to venipuncture.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Medical Research, Inc.	St. Charles	Missouri	United States	63301

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Ali Ziaee, MD, Cetero Research, San Antonio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00846885
• Other Study ID Numbers: 04225
• First Posted: Feb 19, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Test (Sumatriptan) First	Reference (Imitrex®) First
Arm/Group Description	100 mg Sumatriptan Tablets test product dosed in first period followed by 100 mg Imitrex® Tablets reference product dosed in the second period.	100 mg Imitrex® Tablets reference product dosed in first period followed by 100 mg Sumatriptan Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Test (Sumatriptan) First	Reference (Imitrex®) First	Total
Arm/Group Description	100 mg Sumatriptan Tablets test product dosed in first period followed by 100 mg Imitrex® Tablets reference product dosed in the second period.	100 mg Imitrex® Tablets reference product dosed in first period followed by 100 mg Sumatriptan Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	14	14	28
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 100%	14 100%	28 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 42.9%	3 21.4%	9 32.1%
Male	8 57.1%	11 78.6%	19 67.9%
Race/Ethnicity, Customized (participants) [Number]
Asian	0 0%	1 7.1%	1 3.6%
Black	3 21.4%	7 50%	10 35.7%
White	11 78.6%	6 42.9%	17 60.7%
Region of Enrollment (participants) [Number]
United States	14 100%	14 100%	28 100%

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 12 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Sumatriptan)	Reference (Imitrex®)
Arm/Group Description	100 mg Sumatriptan Tablets test product dosed in either period.	100 mg Imitrex® Tablets reference product dosed in either period.
Measure Participants	28	28
Mean (Standard Deviation) [ng/mL]	80.334 (43.6)	71.483 (32.193)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Sumatriptan), Reference (Imitrex®)
	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	110
	Confidence Interval	() 90%; 103 to 117
	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 12 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Sumatriptan)	Reference (Imitrex®)
Arm/Group Description	100 mg Sumatriptan Tablets test product dosed in either period.	100 mg Imitrex® Tablets reference product dosed in either period.
Measure Participants	28	28
Mean (Standard Deviation) [ng*h/mL]	305.374 (116.446)	288.099 (109.217)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Sumatriptan), Reference (Imitrex®)
	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	106
	Confidence Interval	() 90%; 102 to 111
	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 12 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Sumatriptan)	Reference (Imitrex®)
Arm/Group Description	100 mg Sumatriptan Tablets test product dosed in either period.	100 mg Imitrex® Tablets reference product dosed in either period.
Measure Participants	28	28
Mean (Standard Deviation) [ng*h/mL]	314.996 (117.628)	298.953 (111.361)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Sumatriptan), Reference (Imitrex®)
	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	105
	Confidence Interval	() 90%; 101 to 110
	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.