A Dose Escalation Study of a Combination Antihypertensive Drug in the Treatment of Various Groups of Patients Who do Not Respond to Single Drug Treatment of Their High Blood Pressure (BP CRUSH)

This study has been completed.

Sponsor:

Collaborator:

Integrium

Information provided by:

Daiichi Sankyo Inc.

ClinicalTrials.gov Identifier:

NCT00791258

First received: November 13, 2008

Last updated: September 30, 2010

Last verified: September 2010

History of Changes

Results First Received: September 2, 2010

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Hypertension
Interventions:	Drug: amlodipine and olmesartan medoxomil tablets Drug: hydrochlorothiazide tablets

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment occurred at approximately 140 outpatient medical clinics in the United States and South Africa from December 2008 through March 2009. 1406 uncontrolled hypertensive subjects were screened to place 999 subjects into active treatment.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Olmesartan Medoxomil/Amlodipine Tablets + Hydrochlorothiazide	Amlodipine and olmesartan medoxomil (Azor) oral tablets and hydrochlorothiazide oral tablets (if necessary) will be administered once a day for up to 20 weeks

Participant Flow: Overall Study

	Olmesartan Medoxomil/Amlodipine Tablets + Hydrochlorothiazide
STARTED	999
COMPLETED	736
NOT COMPLETED	263
Adverse Event	87
Lost to Follow-up	18
Protocol Violation	109
Withdrawal by Subject	40
Did not take medication for >3 days	1
subject left area	2
non-compliance	3
Subject incarcerated	1
Subject required restricted medication	1
Lack of Efficacy	1

Baseline Characteristics

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Reporting Groups

	Description
Olmesartan Medoxomil/Amlodipine Tablets + Hydrochlorothiazide	Amlodipine and olmesartan medoxomil (Azor) oral tablets and hydrochlorothiazide oral tablets (if necessary) will be administered once a day for up to 20 weeks

Baseline Measures

	Olmesartan Medoxomil/Amlodipine Tablets + Hydrochlorothiazide
Number of Participants [units: participants]	999
Age [units: participants]
<=18 years	0
Between 18 and 65 years	771
>=65 years	228
Gender [units: participants]
Female	491
Male	508
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	6
Asian	129
Native Hawaiian or Other Pacific Islander	0
Black or African American	234
White	630
More than one race	0
Unknown or Not Reported	0
Region of Enrollment [units: participants]
United States	732
South Africa	267
Hispanic or Latino [units: Participants]
Hispanic or Latino	105
Non-Hispanic or Latino	894
Type 2 Diabetes [units: Participants]
Yes	192
No	807
Weight [units: kg] Mean ± Standard Deviation	88.20 ± 21.466
Body Mass Index [units: Kg/m٨2] Mean ± Standard Deviation	31.02 ± 6.370
Metabolic syndrome ^[1] [units: Participants]
Yes	462
No	537
Mean seated systolic blood pressure [units: mm Hg] Mean ± Standard Deviation	153.66 ± 9.178
Mean seated diastolic blood pressure [units: mm Hg] Mean ± Standard Deviation	91.92 ± 8.616
Pulse rate [units: beats/minute] Mean ± Standard Deviation	74.77 ± 11.621
24-Hour mean systolic ambulatory blood pressure [units: mm Hg] Mean ± Standard Deviation	135.74 ± 11.698
24-Hour mean diastolic ambulatory blood pressure [units: mm Hg] Mean ± Standard Deviation	81.09 ± 9.346

[1]	Metabolic syndrome is defined as having at least 3 of the following parameters: waist circumference ≥40 inches (males) or ≥35 inches (females); triglycerides ≥150 mg/dL; high density lipoprotein cholesterol <40 mg/dL (males) or <50 mg/dL (females); blood pressure ≥130/85 mmHg; fasting glucose ≥100mg/dL; BMI ≥30kg/m2.

Outcome Measures

Show All Outcome Measures

1. Primary:

The Percentage of Patients Who Achieve Seated Systolic Blood Pressure Goal (<140 mm Hg for Non-diabetics and <130 mm Hg for Diabetics) From Baseline to 12 Weeks [ Time Frame: baseline to 12 weeks ]

Show Outcome Measure 1

2. Secondary:

The Percentage of Subjects Achieving Seated Diastolic BP Goal (<90 mmHg for Non-diabetics or < 80 mmHg for Subjects With Diabetes) From Baseline to 12 Weeks [ Time Frame: baseline to 12 weeks ]

Show Outcome Measure 2

3. Secondary:

The Percentage of Subjects Who Achieve BP Goal (<140/90 mmHg for Non-diabetics or <130/80 mmHg for Diabetics) From Baseline to 12 and 20 Weeks [ Time Frame: Baseline to 12 and 20 weeks ]

Show Outcome Measure 3

4. Secondary:

Change in Mean Seated Systolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 4

5. Secondary:

Change in Mean Seated Diastolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 5

6. Secondary:

Percentage of Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Hide Outcome Measure 6

Measure Type	Secondary
Measure Title	Percentage of Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks
Measure Description	No text entered.
Time Frame	Baseline to 4, 8, 12, 16, 20 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population consists of those participants who have a baseline and at least 1 post-baseline measurement and who received at least one dose of study medication. However, the number of participants included will vary because of missing data and the number of dropouts.

Reporting Groups

	Description
Olmesartan Medoxomil/Amlodipine Tablets + Hydrochlorothiazide	Amlodipine and olmesartan medoxomil (Azor) oral tablets and hydrochlorothiazide oral tablets (if necessary) will be administered once a day for up to 20 weeks

Measured Values

	Olmesartan Medoxomil/Amlodipine Tablets + Hydrochlorothiazide
Number of Participants Analyzed [units: participants]	975
Percentage of Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [units: Percentage of participants]
4 weeks: <90 mm Hg, N=975	71.3
4weeks: <85 mm Hg, N=975	55.2
4 weeks: <80 mm Hg, N=975	34.2
8 weeks: <90 mm Hg, N=929	75.1
8 weeks: <85 mm Hg, N=929	57.1
8 weeks: <80 mm Hg, N=929	40.2
12 weeks: <90 mm Hg, N=865	84.3
12 weeks: <85 mm Hg, N=865	68.7
12 weeks: <80 mm Hg, N=865	49.5
16 weeks: <90 mm Hg, N=797	90.2
16 weeks: <85 mm Hg, N=797	76.9
16 weeks: <80 mm Hg, N=797	59.6
20 weeks: <90 mm Hg, N=745	89.7
20 weeks: <85 mm Hg, N=745	79.5
20 weeks: <80 mm Hg, N=745	62.0

No statistical analysis provided for Percentage of Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks

7. Secondary:

Percentage of Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 7

8. Secondary:

Percentage of Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 8

9. Secondary:

Percentage of Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 9

10. Secondary:

Percentage of Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 10

11. Secondary:

Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 11

12. Secondary:

Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 12

13. Secondary:

Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 13

14. Secondary:

Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 14

15. Secondary:

Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 15

16. Secondary:

Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 16

17. Secondary:

Change From Baseline to Week 12 in Ambulatory Systolic and Diastolic Blood Pressure Values [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 17

18. Secondary:

Change From Baseline to Week 20 in Ambulatory Systolic and Diastolic Blood Pressure Values [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 18

19. Secondary:

Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 19

20. Secondary:

Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 20

21. Secondary:

Percentage of African American/Black Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 21

22. Secondary:

Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 22

23. Secondary:

Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 23

24. Secondary:

Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 24

25. Secondary:

Percentage of Asain Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 25

26. Secondary:

Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 26

27. Secondary:

Percentage of Asian Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 27

28. Secondary:

Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 28

29. Secondary:

Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 29

30. Secondary:

Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 30

31. Secondary:

Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 31

32. Secondary:

Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 32

33. Secondary:

Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 33

34. Secondary:

Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 34

35. Secondary:

Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 35

36. Secondary:

Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 36

37. Secondary:

Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 37

38. Secondary:

Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 38

39. Secondary:

Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 39

40. Secondary:

Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 40

41. Secondary:

Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 41

42. Secondary:

Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 42

43. Secondary:

Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 43

44. Secondary:

Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 44

45. Secondary:

Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 45

46. Secondary:

Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 46

47. Secondary:

Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ]

Show Outcome Measure 47

48. Secondary:

Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 48

49. Secondary:

Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 49

50. Secondary:

Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 50

51. Secondary:

Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 51

52. Secondary:

Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 52

53. Secondary:

Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 53

54. Secondary:

Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 54

55. Secondary:

Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 55

56. Secondary:

Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 56

57. Secondary:

Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 57

58. Secondary:

Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Show Outcome Measure 58

59. Secondary:

Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ]

Show Outcome Measure 59

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: As stated in the clinical study agreement, If identified by DSI, any of DSI's confidential information as defined herein shall be deleted...Nothing in this publication section shall be taken as giving DSI any right of editorial control over any publicartion prepared by the Study Site."

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: John Raia
Organization: Daiichi Sankyo, Inc
phone: (973) 944-2683
e-mail: jraia@dsi.com

No publications provided by Daiichi Sankyo Inc.

Publications automatically indexed to this study:

Hsueh WA, Shojaee A, Maa JF, Neutel JM. Efficacy of amlodipine/olmesartan medoxomil ± HCTZ in obese patients uncontrolled on antihypertensive monotherapy. Curr Med Res Opin. 2012 Nov;28(11):1809-18. doi: 10.1185/03007995.2012.740632. Epub 2012 Oct 30.

Responsible Party:	Diector of Medical Research and Strategy, Daiichi Sankyo
ClinicalTrials.gov Identifier:	NCT00791258 History of Changes
Other Study ID Numbers:	CS8663-404
Study First Received:	November 13, 2008
Results First Received:	September 2, 2010
Last Updated:	September 30, 2010
Health Authority:	United States: Food and Drug Administration

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