Safety and Tolerability of Trospium Chloride and Metformin Hydrochloride in Healthy Subjects

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00986401
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 43.2

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and tolerability of trospium chloride (Sanctura XR™) and metformin hydrochloride (Glucophage) when co-administered.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Trospium Chloride (Sanctura XR®); Drug: Metformin hydrochloride (Glucophage®)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: Safety and Tolerability of Trospium Chloride Metformin Hydrochloride in Healthy Subjects
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glucophage® then Sanctura XR® (AB) Treatment Period 1: Glucophage® (500 mg, BID) for 3.5 days. Washout: There will be a washout period of 3 days between each treatment period. Treatment Period 2: Sanctura XR® (60 mg, QD) for 10 days followed by Sanctura XR® (60 mg, QD) for 4 days + Glucophage® (500 mg, BID) for 3.5 days.	Drug: Metformin hydrochloride (Glucophage®); immediate release, 500mg; Other Names: Glucophage®
Experimental: Sanctura XR® then Glucophage® (BA) Treatment Period 1: Sanctura XR® (60 mg, QD) for 10 days followed by Sanctura XR® (60 mg, QD for 4 days) + Glucophage® (500 mg, BID) for 3.5 days. Washout: There will be a washout period of 3 days between each treatment period. Treatment Period 2: Glucophage® (500 mg, BID) for 3.5 days.	Drug: Trospium Chloride (Sanctura XR®); extended release, 60 mg, oral daily; Other Names: Sanctura XR® 60 mg

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Level (Cmax) of Metformin Hydrochloride (Glucophage®) Following Oral Administration of Glucophage® [34 Days]

   Maximum Plasma Level (Cmax) of Metformin Hydrochloride (Glucophage®) following oral administration of Glucophage® alone and in combination with SanturaXR®. Plasma is the fluid portion of the blood.

Secondary Outcome Measures

1. Maximum Plasma Level (Cmax) of Trospium Chloride (Sanctura XR®) Following Oral Administration of Sanctura XR® [34 Days]

   Maximum Plasma Level (Cmax) of Trospium Chloride (Sanctura XR®) Following Oral Administration of Sanctura XR® alone and in combination with Glucophage®. Plasma is the fluid portion of the blood in which the cells are suspended.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Weight within +/-30% of ideal body weight for height and frame size

• Non-smoker (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc., for 1 months prior to the screening visit).

• Willing to abstain from caffeine-containing food and beverages for 24-hours prior to dosing, alcohol-containing food and beverage for 48 hours prior to dosing, and Seville oranges (eg orange marmalade), grapefruit, or grapefruit juice for 7 days prior to the dosing and abstain from all throughout the study.

• Willing to abstain from taking medications (with the exception of hormonal contraceptives) and nonprescription medication including vitamins, food supplements, and herbal preparations for 7 days prior to Day-1 of the first treatment period and throughout the study.

Exclusion Criteria:

• Uncontrolled systemic disease

• Known allergy or sensitivity to the study medication(s) (Trospium, Metformin)or its components

• Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study.

• History of myasthenia gravis or closed-angle glaucoma.

• Considering or scheduled to undergo any surgical procedure during the study.

• History of alcohol or substance abuse within 1 year prior to Day-1 of the first treatment period.

• History of serious mental or physical illness.

• Donated in excess of 500 mL of blood in the 30 days prior to the screening visit.

• Required treatment with any medications, either prescription or nonprescription (including vitamins, antacids, acid-reducers, food supplements, and herbal preparations, excluding hormonal contraceptives), within 7 days prior to Day-1 of the first treatment period during the study.

• Had an acute illness within 5 days prior to Day-1 of the treatment period.

• Had a history of hepatitis B or C, a positive test for hepatitis B surface antigen, hepatitis C antibody, a history of human immunodeficiency virus (HIV) infection or demonstration of HIV antibodies.

• Planned radiologic study requiring intravenous contrast administration of iodinated contrast material during the study period Serum Creatinine greater than 1.4 mg/dL.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tempe	Arizona	United States

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT00986401
• Other Study ID Numbers: MA-SXR-09-002
• First Posted: Sep 30, 2009
• Last Update Posted: Dec 19, 2011
• Last Verified: Nov 1, 2011

• Keywords provided by Allergan: Adults
• Additional relevant MeSH terms: Metformin; Trospium chloride

Study Results

Participant Flow

Arm/Group Title	Glucophage® Then Sanctura XR® (AB)	Sanctura XR® Then Glucophage® (BA)
Arm/Group Description	Treatment Period 1: Glucophage® (500 mg, BID) for 3.5 days. Washout: There will be a washout period of 3 days between each treatment period. Treatment Period 2: Sanctura XR® (60 mg, QD) for 10 days followed by Sanctura XR® (60 mg, QD) for 4 days + Glucophage® (500 mg, BID) for 3.5 days.	Treatment Period 1: Sanctura XR® (60 mg, QD) for 10 days followed by Sanctura XR® (60 mg, QD for 4 days) + Glucophage® (500 mg, BID) for 3.5 days. Washout: There will be a washout period of 3 days between each treatment period. Treatment Period 2: Glucophage® (500 mg, BID) for 3.5 days.
Period Title: Period 1
STARTED	22	22
COMPLETED	22	21
NOT COMPLETED	0	1
Period Title: Period 1
STARTED	22	21
COMPLETED	22	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Glucophage® Then Sanctura XR® (AB)	Sanctura XR® Then Glucophage® (BA)	Total
Arm/Group Description	Treatment Period 1: Glucophage® (500 mg, BID) for 3.5 days. Washout: There will be a washout period of 3 days between each treatment period. Treatment Period 2: Sanctura XR® (60 mg, QD) for 10 days followed by Sanctura XR® (60 mg, QD) for 4 days + Glucophage® (500 mg, BID) for 3.5 days.	Treatment Period 1: Sanctura XR® (60 mg, QD) for 10 days followed by Sanctura XR® (60 mg, QD for 4 days) + Glucophage® (500 mg, BID) for 3.5 days. Washout: There will be a washout period of 3 days between each treatment period. Treatment Period 2: Glucophage® (500 mg, BID) for 3.5 days.	Total of all reporting groups
Overall Participants	22	22	44
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	31.0	30.2	31.0
Sex: Female, Male (Count of Participants)
Female	10 45.5%	9 40.9%	19 43.2%
Male	12 54.5%	13 59.1%	25 56.8%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Level (Cmax) of Metformin Hydrochloride (Glucophage®) Following Oral Administration of Glucophage®
Description	Maximum Plasma Level (Cmax) of Metformin Hydrochloride (Glucophage®) following oral administration of Glucophage® alone and in combination with SanturaXR®. Plasma is the fluid portion of the blood.
Time Frame	34 Days

Outcome Measure Data

Analysis Population Description

Intent-to-treat, which includes all patients who started the study (randomized). One patient was not included in the analysis due to early discontinuation.

Arm/Group Title	Glucophage®	Glucophage® + Sanctura XR®
Arm/Group Description	Glucophage®	Glucophage® + Sanctura XR®
Measure Participants	43	43
Mean (Standard Deviation) [Nanograms per milliliter (ng/mL)]	739 (263)	753 (252)

2. Secondary Outcome

Title	Maximum Plasma Level (Cmax) of Trospium Chloride (Sanctura XR®) Following Oral Administration of Sanctura XR®
Description	Maximum Plasma Level (Cmax) of Trospium Chloride (Sanctura XR®) Following Oral Administration of Sanctura XR® alone and in combination with Glucophage®. Plasma is the fluid portion of the blood in which the cells are suspended.
Time Frame	34 Days

Outcome Measure Data

Analysis Population Description

Intent-to-treat, which includes all patients who started the study (randomized). One patient was not included in the analysis due to early discontinuation.

Arm/Group Title	Sanctura XR®	Sanctura XR® + Glucophage®
Arm/Group Description	Sanctura XR®	Sanctura XR® + Glucophage®
Measure Participants	44	43
Mean (Standard Deviation) [Nanograms per milliliter (ng/mL)]	1.87 (1.44)	1.17 (0.71)

Adverse Events

Adverse Event Reporting Description	The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Arm/Group Title	Glucophage®		Sanctura XR®		Sanctura XR® in Combination With Glucophage®
Arm/Group Description	Glucophage®		Sanctura XR®		Sanctura XR® in combination with Glucophage®
All Cause Mortality
	Glucophage®		Sanctura XR®		Sanctura XR® in Combination With Glucophage®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Glucophage®		Sanctura XR®		Sanctura XR® in Combination With Glucophage®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/44 (0%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	Glucophage®		Sanctura XR®		Sanctura XR® in Combination With Glucophage®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/43 (23.3%)		3/44 (6.8%)		13/44 (29.5%)
Gastrointestinal disorders
Abdominal pain upper	3/43 (7%)		0/44 (0%)		0/44 (0%)
Diarrhoea	3/43 (7%)		0/44 (0%)		3/44 (6.8%)
Nervous system disorders
Headache	4/43 (9.3%)		3/44 (6.8%)		7/44 (15.9%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/43 (0%)		0/44 (0%)		3/44 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.