Determine the Bioequivalence of Two Formulations of Tamsulosin HCl Capsules in Fasted Male.

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02417831
• Collaborator: (none)
• Enrollment: 34
• Arms: 2
• Actual Duration (Months): 1

Study Details

Study Description

Brief Summary

A bio-equivalence of 2 different capsule formulations in fasted subjects

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hyperplasia	Drug: tamsulosin capsules; Drug: tamsulosin HCl	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single Center, Single Dose, Open-label, Randomized, Two-way Crossover Study to Determine Bioequivalence of Two Formulations Containing Tamsulosin HCl 04.mg MR Capsules in at Least 30 Healthy Male Subjects Under Fasted Conditions
• Actual Study Start Date: Apr 30, 2015
• Actual Primary Completion Date: May 31, 2015
• Actual Study Completion Date: May 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: tamsulosin capsules	Drug: tamsulosin capsules
Active Comparator: tamsulosin HCl capsules	Drug: tamsulosin HCl

Outcome Measures

Primary Outcome Measures

1. Cmax [Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.]

   Maximum measured concentration in plasma (Cmax). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.

2. AUC0-tz [Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.]

   Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.

3. (AUC0-inf) [Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.]

   Area under the concentration-time curve of analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.

Secondary Outcome Measures

1. Tmax [Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.]

   Time to maximum plasma concentration

2. λz [Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.]

   Terminal elimination rate constant in plasma (λz). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.

3. t1/2 [Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.]

   Apparent terminal elimination half-life of the analyte in plasma (t1/2) Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

Healthy male volunteers 18 years and older

Exclusion criteria:

History of hypersensitivity or allergy to the IPM or its excipients or any related medication

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02417831
• Other Study ID Numbers: 527.88
• First Posted: Apr 16, 2015
• Last Update Posted: Apr 27, 2020
• Last Verified: Apr 1, 2020

• Additional relevant MeSH terms: Prostatic Hyperplasia; Hyperplasia; Tamsulosin

Study Results

Participant Flow

Arm/Group Title	New MR (Test) / Registered MR (Reference)	Registered MR (Reference) / New MR (Test)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule followed by oral administration of tamsulosin registered 0.4mg MR capsule in the fasted state after an overnight fast of at least 10 hours. Treatment periods were separated by a wash-out period of 07 days.	Oral administration of tamsulosin registered 0.4mg MR capsule followed by oral administration of tamsulosin new 0.4mg MR capsule in the fasted state after an overnight fast of at least 10 hours. Treatment periods were separated by a wash-out period of 07 days.
Period Title: Period 1: Treatment Period 1 + Washout
STARTED	17	17
COMPLETED	17	17
NOT COMPLETED	0	0
Period Title: Period 1: Treatment Period 1 + Washout
STARTED	17	17
COMPLETED	17	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	Subjects each received two treatments which were each administered orally in the fasted state after an overnight fast of at least 10 hours. and separated by a washout period of 7 days. The treatments were: New MR (Test): Tamsulosin 0.4mg modified release (MR) capsule. Registered MR (Reference) : Tamsulosin 0.4mg capsule.
Overall Participants	34
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	25.4 (5.75)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	34 100%

Outcome Measures

1. Primary Outcome

Title	Cmax
Description	Maximum measured concentration in plasma (Cmax). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.
Time Frame	Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set (PK set): All subjects who had evaluable pharmacokinetic (PK) data for both treatment periods were included in the statistical PK analysis for the study.

Arm/Group Title	New MR (Test)	Registered MR (Reference)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule.	Oral administration of tamsulosin registered 0.4mg MR capsule.
Measure Participants	34	34
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	21700 (37.8)	20520 (36.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	New MR (Test), Registered MR (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Bioequivalence range of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	105.76
	Confidence Interval	(2-Sided) 90%; 99.81 to 112.08
	Parameter Dispersion	Type: Standard Deviation; Value: 14.18
	Estimation Comments	The standard deviation in the statistical analysis is actually the intra-individual coefficient of variation. Ratio calculated as test divided by reference.

2. Primary Outcome

Title	AUC0-tz
Description	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.
Time Frame	Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.

Outcome Measure Data

Analysis Population Description

PK set

Arm/Group Title	New MR (Test)	Registered MR (Reference)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule.	Oral administration of tamsulosin registered 0.4mg MR capsule.
Measure Participants	34	34
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	241500 (48.4)	238200 (48.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	New MR (Test), Registered MR (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Bioequivalence range of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	101.40
	Confidence Interval	(2-Sided) 90%; 97.71 to 105.23
	Parameter Dispersion	Type: Standard Deviation; Value: 9.05
	Estimation Comments	The standard deviation in the statistical analysis is actually the intra-individual coefficient of variation. Ratio calculated as test divided by reference.

3. Primary Outcome

Title	(AUC0-inf)
Description	Area under the concentration-time curve of analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.
Time Frame	Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.

Outcome Measure Data

Analysis Population Description

PK set

Arm/Group Title	New MR (Test)	Registered MR (Reference)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule.	Oral administration of tamsulosin registered 0.4mg MR capsule.
Measure Participants	34	34
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	248200 (49.4)	244700 (48.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	New MR (Test), Registered MR (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Bioequivalence range of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	101.42
	Confidence Interval	(2-Sided) 90%; 97.81 to 105.17
	Parameter Dispersion	Type: Standard Deviation; Value: 8.85
	Estimation Comments	The standard deviation in the statistical analysis is actually the intra-individual coefficient of variation. Ratio calculated as test divided by reference.

4. Secondary Outcome

Title	Tmax
Description	Time to maximum plasma concentration
Time Frame	Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.

Outcome Measure Data

Analysis Population Description

PK set

Arm/Group Title	New MR (Test)	Registered MR (Reference)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule.	Oral administration of tamsulosin registered 0.4mg MR capsule.
Measure Participants	34	34
Median (Full Range) [Hours]	5.004	5.006

5. Secondary Outcome

Title	λz
Description	Terminal elimination rate constant in plasma (λz). Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.
Time Frame	Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.

Outcome Measure Data

Analysis Population Description

PK set

Arm/Group Title	New MR (Test)	Registered MR (Reference)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule.	Oral administration of tamsulosin registered 0.4mg MR capsule.
Measure Participants	34	34
Geometric Mean (Geometric Coefficient of Variation) [1/hours]	0.05 (28.40)	0.05 (24.10)

6. Secondary Outcome

Title	t1/2
Description	Apparent terminal elimination half-life of the analyte in plasma (t1/2) Geometric Coefficient of Variation (gCV) is actually inter-individual gCV.
Time Frame	Before drug administration (0 hours (h)) and 1h, 2h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration.

Outcome Measure Data

Analysis Population Description

PK set

Arm/Group Title	New MR (Test)	Registered MR (Reference)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule.	Oral administration of tamsulosin registered 0.4mg MR capsule.
Measure Participants	34	34
Geometric Mean (Geometric Coefficient of Variation) [Hours]	13.10 (28.40)	13.52 (24.10)

Adverse Events

Time Frame	From drug administration until 7days thereafter for each treatment arm, upto 10 days.
Arm/Group Title	New MR (Test)		Registered MR (Reference)
Arm/Group Description	Oral administration of tamsulosin new 0.4mg modified release (MR) capsule.		Oral administration of tamsulosin registered 0.4mg MR capsule.
All Cause Mortality
	New MR (Test)		Registered MR (Reference)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	New MR (Test)		Registered MR (Reference)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	New MR (Test)		Registered MR (Reference)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/34 (17.6%)		9/34 (26.5%)
Nervous system disorders
Dizziness	2/34 (5.9%)		5/34 (14.7%)
Headache	3/34 (8.8%)		3/34 (8.8%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/34 (2.9%)		2/34 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.