Efficacy and Safety of Alogliptin Compared to Glipizide in Elderly Diabetics

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00707993
• Collaborator: (none)
• Enrollment: 441
• Locations: 80
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of alogliptin, once daily (QD), compared to glipizide in elderly diabetic patients who have not received treatment or are on a single oral medication.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Drug: Alogliptin; Drug: Glipizide	Phase 3

Detailed Description

Type 2 diabetes is among the most common chronic condition in adults 65 years of age or older. A recent National Health and Nutrition Examination Survey reported that more than 20% of adults aged 65 years or older have diabetes. These individuals are often under-treated with respect to glucose-lowering medications, and their care is complicated by the extent of their clinical and functional status. Age-related changes in physiology, diabetes-associated illnesses and other illnesses (such as renal, cardiac, and hepatic insufficiency), as well as use of multiple medications make standard oral anti-hyperglycemic therapy and insulin use problematic. In addition, hypoglycemia is more common and severe in older rather than younger patients taking oral antidiabetic drugs which can precipitate serious events such as falls and hip fractures. While avoidance of hypoglycemia is paramount in elderly diabetic patients, many commonly used medications are associated with a substantial risk for hypoglycemia. New classes of drug which avoid such complications in the elderly population are of increasing interest as this population continues to expand.

Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes.

This study will compare the effectiveness and safety of alogliptin with that of glipizide (a commonly used diabetes medication) in adults who are 65 to 90 years of age with Type 2 diabetes. Individuals who participate in this study will either have failed diet and exercise therapy alone during the 2 months before Screening, or will have been receiving a single oral antidiabetic medication without obtaining good blood glucose (sugar) control.

Each participant will be required to commit to screening visits. Study participation is anticipated to be up to 59 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 441 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Alogliptin Compared to Glipizide in Elderly Subjects With Type 2 Diabetes
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alogliptin 25 mg QD	Drug: Alogliptin; Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.; Other Names: SYR110322 SYR-322
Active Comparator: Glipizide 5 mg QD	Drug: Glipizide; Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.; Other Names: Glucotrol

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin at Week 52. [Baseline and Week 52.]

   The change in the percentage of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 or final visit and glycosylated hemoglobin collected at baseline.

Secondary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin [Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34 and Week 42.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated including final visit relative to baseline.

2. Incidence of Hypoglycemia [On occurrence (up to 52 weeks).]

   Percentage of participants with at least one hypoglycemic episode during 52 week study.

3. Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). [On Occurrence (up to 52 weeks).]

   The number of participants with a fasting plasma glucose value ≥ to 200 mg per dL during the 52 week study.

4. Incidence of Hyperglycemic Rescue [On Occurrence (up to 52 weeks).]

   The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 52 week study.

5. Change From Baseline in Fasting Plasma Glucose [Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34, Week 42 and Week 52.]

   The change in the value of fasting plasma glucose collected at each week indicated including final visit relative to baseline.

6. Change From Baseline in 2-hour Postprandial Glucose [Baseline and Week 52.]

   The change in postprandial (after eating a meal) glucose levels at week 52 relative to baseline. Standard 2-hour postprandial glucose (PPG) tests performed following an overnight fast and evaluated right before and after a 120-minute (2-hour) timeframe relative to ingestion of a standard oral glucose drink.

7. Change From Baseline in Fasting Proinsulin [Baseline, Week 12, Week 26, Week 42 and Week 52.]

   The change between the value of fasting proinsulin collected at each week indicated including final visit relative to baseline.

8. Change From Baseline in Insulin [Baseline, Week 12, Week 26, Week 42 and Week 52.]

   The change between the value of insulin collected at each week indicated including final visit relative to baseline.

9. Change From Baseline in Proinsulin/Insulin Ratio [Baseline, Week 12, Week 26, Week 42 and Week 52.]

   The change between the ratio value of proinsulin and insulin collected at each week indicated including final visit relative to baseline.

10. Homeostasis Model Assessment of Beta Cell Function [Baseline, Week 12, Week 26, Week 42 and Week 52.]

    The change between homeostasis model assessment of beta cell function collected at each week indicated including final visit relative to baseline. Homeostasis model assessment of beta cell function measures beta cell function, calculated by a constant (20) times insulin, divided by fasting plasma glucose minus a constant (3.5).

11. Change From Baseline in Body Weight [Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.]

    The change in body weight measured at each week indicated including final visit from baseline.

12. Change From Baseline in Serum Lipids (Total Cholesterol) [Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.]

    The change in total cholesterol measured at each week indicated including final visit from baseline.

13. Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) [Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.]

    The change in high-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.

14. Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) [Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.]

    The change in low-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.

15. Change From Baseline in Serum Lipids (Triglycerides) [Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.]

    The change in triglycerides measured at each week indicated including final visit from baseline.

16. Change From Baseline in High Sensitivity C-reactive Protein [Baseline, Week 12, Week 26, Week 42 and Week 52.]

    The change between the high sensitivity C-reactive protein value collected at each week indicated including final visit from baseline.

17. Incidence of Subjects Achieving Glycosylated Hemoglobin <=7% [Baseline and Week 52.]

    The percentage of participants with a value for the percentage of glycosylated hemoglobin (HbA1c; the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5 and 7.0% during the 52 week study.

18. Incidence of Glycosylated Hemoglobin Decrease From Baseline. [Baseline and Week 52.]

    The percentage of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5, 1.0, 1.5 and 2.0% during the 52 week study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has a diagnosis of type 2 diabetes mellitus with either:

• Failed diet and exercise therapy alone as demonstrated by inadequate glycemic control while receiving no antidiabetic treatment within the two months prior to Screening, or

• Failed treatment with oral monotherapy alone (may include treatment with two or more antidiabetic agents if for less than 7 days) as demonstrated by inadequate glycemic control within the two months prior to Screening.

• Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2.

• If regularly using other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening.

• Females of childbearing potential who are sexually active must agree to use a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

• Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.

• No major illness or debility that in the investigator's opinion prohibits the participant from completing the study.

Exclusion Criteria:

• Systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic pressure greater than or equal to 100 mm Hg.

• Hemoglobin less than or equal to 12 g/dL for males or less than or equal to 10 g/dL for females.

• Alanine aminotransferase greater than or equal to 3 times the upper limit of normal.

• Calculated creatinine clearance less than or equal to 50 mL/min.

• Thyroid-stimulating hormone level outside of the normal range.

• History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening.

• History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.

• History of treated diabetic gastroparesis, gastric banding, or gastric bypass surgery.

• New York Heart Association Class III or IV heart failure regardless of therapy.

• History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening.

• History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.

• History of infection with Human Immunodeficiency Virus.

• History of a psychiatric disorder that will affect the participant's ability to participate in the study.

• History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.

• History of alcohol or substance abuse within the 2 years prior to Screening.

• History of treatment with any weight-loss drugs or oral or systemically injected glucocorticoids within the 3 months prior to Screening.

• Receipt of any investigational drug within the 30 days prior to Screening.

• Prior treatment in an investigational study of alogliptin.

• Clinically significant medical abnormality or disease or clinically significant abnormal findings at Screening (other than type 2 diabetes) that, in the opinion of the investigator, should exclude the participant from the study.

• Has donated more than 400 mL of blood within the 90 days preceding their participation in the study.

• Has hypersensitivity or has had an anaphylactic reaction(s) to any DPP-4 inhibitor drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Alexander City	Alabama	United States
2		Foothill Ranch	California	United States
3		Huntington Park	California	United States
4		Long Beach	California	United States
5		Los Angeles	California	United States
6		Redlands	California	United States
7		Prospect	Connecticut	United States
8		Bradenton	Florida	United States
9		Fort Myers	Florida	United States
10		Miami	Florida	United States
11		Ormond Beach	Florida	United States
12		Winter Park	Florida	United States
13		Roswell	Georgia	United States
14		Aurora	Illinois	United States
15		LaPorte	Indiana	United States
16		South Bend	Indiana	United States
17		Salisbury	Maryland	United States
18		Clarkston	Michigan	United States
19		Omaha	Nebraska	United States
20		Hamilton	New Jersey	United States
21		Albuquerque	New Mexico	United States
22		Beachwood	Ohio	United States
23		Westlake	Ohio	United States
24		Zanesville	Ohio	United States
25		Bensalem	Pennsylvania	United States
26		Aiken	South Carolina	United States
27		Greenville	South Carolina	United States
28		Greer	South Carolina	United States
29		Taylors	South Carolina	United States
30		Corpus Christi	Texas	United States
31		Dallas	Texas	United States
32		Pasadena	Texas	United States
33		San Antonio	Texas	United States
34		Tomball	Texas	United States
35		Ogden	Utah	United States
36		Salt Lake City	Utah	United States
37		Budapest		Hungary
38		Miskoic		Hungary
39		Nyiregyhaza		Hungary
40		Karnal	Haryana	India
41		Bangalore	Karnataka	India
42		Belgaum	Karnataka	India
43		Mumbai	Maharashrta	India
44		Ashkelon		Israel
45		Haifa		Israel
46		Holon		Israel
47		Nahariya		Israel
48		Rishon Le-Zion		Israel
49		Zefat		Israel
50		Saltillo	Coahuila	Mexico
51		Pachuca	Hidalgo	Mexico
52		Morelia	Michoacan	Mexico
53		Monterrey	Nuevo Leon	Mexico
54		Aguascalientes		Mexico
55		Durango		Mexico
56		Guadalajara		Mexico
57		Mexico DF		Mexico
58		Nezahualcoyotl		Mexico
59		Arequipa		Peru
60		Lima		Peru
61		Piura		Peru
62		Gdansk		Poland
63		Krakow		Poland
64		Warszawa		Poland
65		Baia Mare		Romania
66		Brasov		Romania
67		Bucharest		Romania
68		Galati		Romania
69		Satu Mare		Romania
70		Arkhangelsk		Russian Federation
71		Irkutsk		Russian Federation
72		Smolensk		Russian Federation
73		Cape Town		South Africa
74		Centurion		South Africa
75		Durban		South Africa
76		Johannesburg		South Africa
77		Port Elizabeth		South Africa
78		Pretoria		South Africa
79		Donetsk		Ukraine
80		Kharkiv		Ukraine

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: VP Biological Sciences, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00707993
• Other Study ID Numbers: SYR-322_303; 2008-000959-10; U1111-1112-7905
• First Posted: Jul 2, 2008
• Last Update Posted: May 24, 2013
• Last Verified: May 1, 2013

• Keywords provided by Takeda: Glucose Metabolism Disorder; Dysmetabolic Syndrome; Type II Diabetes; Diabetes Mellitus; Lipoatrophic; Dyslipidemia; Drug Therapy
• Additional relevant MeSH terms: Diabetes Mellitus; Alogliptin; Glipizide

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 110 investigative sites in Hungary, India, Israel, Mexico, Peru, Poland, Romania, Russia, South Africa, the Ukraine and the United States from 25 June 2008 to 30 August 2010.
Pre-assignment Detail	Participants with a historical diagnosis of type 2 diabetes mellitus were enrolled in one of two, once-daily (QD) treatment groups.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Period Title: Overall Study
STARTED	222	219
COMPLETED	133	125
NOT COMPLETED	89	94

Baseline Characteristics

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD	Total
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.	Total of all reporting groups
Overall Participants	222	219	441
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.1 (4.42)	69.8 (4.07)	69.9 (4.24)
Age, Customized (participants) [Number]
<75 years	186 83.8%	193 88.1%	379 85.9%
≥75 years	36 16.2%	26 11.9%	62 14.1%
Sex: Female, Male (Count of Participants)
Female	120 54.1%	123 56.2%	243 55.1%
Male	102 45.9%	96 43.8%	198 44.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	79 35.6%	70 32%	149 33.8%
Not Hispanic or Latino	143 64.4%	149 68%	292 66.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	12 5.4%	13 5.9%	25 5.7%
Asian	19 8.6%	26 11.9%	45 10.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	16 7.2%	20 9.1%	36 8.2%
White	169 76.1%	154 70.3%	323 73.2%
More than one race	6 2.7%	6 2.7%	12 2.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	78.60 (14.842)	78.81 (15.239)	78.70 (15.024)
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	29.58 (4.348)	30.02 (4.459)	29.79 (4.404)
Diabetes duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.25 (6.285)	5.94 (6.276)	6.10 (6.275)
Glomerular Filtration Rate (GFR) (mL/min/1.73 m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73 m2]	73.62 (14.762)	72.89 (15.524)	73.26 (15.133)
Smoking history (participants) [Number]
Never smoked	160 72.1%	168 76.7%	328 74.4%
Current smoker	16 7.2%	11 5%	27 6.1%
Ex-smoker	46 20.7%	40 18.3%	86 19.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin at Week 52.
Description	The change in the percentage of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 or final visit and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 52.

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug, had measurements at Baseline and at the visit, and who met pre-specified criteria (no major protocol violations) for inclusion in the Per Protocol Set. Missing data were imputed using last observation carried forward (LOCF).

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	180	162
Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]	-0.14 (0.063)	-0.09 (0.067)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alogliptin 25 mg QD, Glipizide 5 mg QD
	Comments	Primary null hypothesis: the average Week 52 HbA1c change from Baseline for alogliptin is inferior to that for glipizide (1-sided 97.5% CI [alpha=0.025] compared to non-inferiority margin of 0.4%). If the primary null hypothesis was rejected (non-inferiority demonstrated), an additional comparison for statistical superiority of alogliptin was performed. The CI was re-evaluated; statistical superiority declared if the upper limit was < 0%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.05
	Confidence Interval	(1-Sided) 97.5%; to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated including final visit relative to baseline.
Time Frame	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34 and Week 42.

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug, had measurements at Baseline and at the visit, and who met pre-specified criteria (no major protocol violations) for inclusion in the Per Protocol Set. Missing data were imputed using last observation carried forward (LOCF).

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	180	162
Week 4 (n=175; n=148)	-0.14 (0.047)	-0.11 (0.051)
Week 8 (n=180; n=161)	-0.27 (0.051)	-0.23 (0.054)
Week 12 (n=180; n=162)	-0.34 (0.053)	-0.25 (0.055)
Week 16 (n=180; n=162)	-0.31 (0.050)	-0.32 (0.052)
Week 20 (n=180; n=162)	-0.31 (0.051)	-0.27 (0.054)
Week 26 (n=180; n=162)	-0.28 (0.052)	-0.25 (0.055)
Week 34 (n=180; n=162)	-0.21 (0.056)	-0.21 (0.059)
Week 42 (n=180; n=162)	-0.17 (0.062)	-0.17 (0.065)

3. Secondary Outcome

Title	Incidence of Hypoglycemia
Description	Percentage of participants with at least one hypoglycemic episode during 52 week study.
Time Frame	On occurrence (up to 52 weeks).

Outcome Measure Data

Analysis Population Description

Percentages based on the number of Safety Set participants in each treatment group.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Number [percentage of participants]	5.4 2.4%	26.0 11.9%

4. Secondary Outcome

Title	Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL).
Description	The number of participants with a fasting plasma glucose value ≥ to 200 mg per dL during the 52 week study.
Time Frame	On Occurrence (up to 52 weeks).

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set).

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Baseline to <Week 4	30 13.5%	17 7.8%
Week 4 to <Week 8	11 5%	5 2.3%
Week 8 to <Week 12	12 5.4%	8 3.7%
Week 12 to <Week 16	11 5%	8 3.7%
Week 16 to <Week 20	5 2.3%	4 1.8%
Week 20 to <Week 26	2 0.9%	3 1.4%
Week 26 to <Week 34	3 1.4%	8 3.7%
Week 34 to <Week 42	2 0.9%	4 1.8%
Week 42 to Week 52	9 4.1%	6 2.7%
Overall	50 22.5%	37 16.9%

5. Secondary Outcome

Title	Incidence of Hyperglycemic Rescue
Description	The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 52 week study.
Time Frame	On Occurrence (up to 52 weeks).

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set). Participants who discontinued prior to Week 2 were excluded from analysis.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 2 to <Week 4	1 0.5%	0 0%
Week 4 to <Week 8	2 0.9%	1 0.5%
Week 8 to <Week 12	1 0.5%	0 0%
Week 12 to <Week 16	14 6.3%	14 6.4%
Week 16 to <Week 20	6 2.7%	9 4.1%
Week 20 to <Week 26	5 2.3%	8 3.7%
Week 26 to <Week 34	10 4.5%	2 0.9%
Week 34 to <Week 42	6 2.7%	7 3.2%
Week 42 to Week 52	10 4.5%	6 2.7%
Overall	50 22.5%	37 16.9%

6. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose
Description	The change in the value of fasting plasma glucose collected at each week indicated including final visit relative to baseline.
Time Frame	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 2 (n=196; n=199)	-3.8 (1.93)	-5.0 (1.91)
Week 4 (n=217; n=213)	-7.7 (1.93)	-7.6 (1.95)
Week 8 (n=217; n=214)	-8.9 (1.76)	-8.7 (1.77)
Week 12 (n=217; n=214)	-10.2 (1.84)	-9.9 (1.86)
Week 16 (n=217; n=214)	-7.9 (1.85)	-11.4 (1.86)
Week 20 (n=217; n=214)	-9.8 (1.78)	-8.7 (1.79)
Week 26 (n=217; n=214)	-7.9 (1.97)	-6.2 (1.99)
Week 34 (n=217; n=214)	-5.4 (1.98)	-5.7 (1.99)
Week 42 (n=217; n=214)	-3.6 (2.13)	-7.4 (2.14)
Week 52 (n=217; n=214)	-2.4 (2.24)	-4.2 (2.26)

7. Secondary Outcome

Title	Change From Baseline in 2-hour Postprandial Glucose
Description	The change in postprandial (after eating a meal) glucose levels at week 52 relative to baseline. Standard 2-hour postprandial glucose (PPG) tests performed following an overnight fast and evaluated right before and after a 120-minute (2-hour) timeframe relative to ingestion of a standard oral glucose drink.
Time Frame	Baseline and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set).

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 52 PPG level (n=109; n=93)	-5.80 (5.530)	6.30 (5.989)
Week 52 PPG excursion (n=109; n=93)	1.82 (4.434)	7.17 (4.804)

8. Secondary Outcome

Title	Change From Baseline in Fasting Proinsulin
Description	The change between the value of fasting proinsulin collected at each week indicated including final visit relative to baseline.
Time Frame	Baseline, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 12 (n=207; n=186)	-6.0 (0.99)	1.0 (1.05)
Week 26 (n=211; n=194)	-4.6 (1.49)	3.0 (1.56)
Week 42 (n=211; n=194)	-4.6 (1.48)	3.1 (1.54)
Week 52 (n=211; n=194)	-4.9 (1.42)	3.0 (1.48)

9. Secondary Outcome

Title	Change From Baseline in Insulin
Description	The change between the value of insulin collected at each week indicated including final visit relative to baseline.
Time Frame	Baseline, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 12 (n=207; n=188)	-2.36 (0.673)	0.84 (0.707)
Week 26 (n=210; n=194)	-0.41 (1.548)	3.03 (1.611)
Week 42 (n=210; n=194)	-0.58 (1.254)	1.53 (1.305)
Week 52 (n=210; n=194)	-1.72 (1.731)	3.15 (1.801)

10. Secondary Outcome

Title	Change From Baseline in Proinsulin/Insulin Ratio
Description	The change between the ratio value of proinsulin and insulin collected at each week indicated including final visit relative to baseline.
Time Frame	Baseline, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 12 (n=206; n=185)	-0.288 (0.1035)	0.053 (0.1092)
Week 26 (n=210; n=193)	-0.253 (0.4333)	0.562 (0.4520)
Week 42 (n=210; n=193)	-0.289 (0.1500)	0.183 (0.1565)
Week 52 (n=210; n=193)	-0.155 (0.0899)	-0.057 (0.0938)

11. Secondary Outcome

Title	Homeostasis Model Assessment of Beta Cell Function
Description	The change between homeostasis model assessment of beta cell function collected at each week indicated including final visit relative to baseline. Homeostasis model assessment of beta cell function measures beta cell function, calculated by a constant (20) times insulin, divided by fasting plasma glucose minus a constant (3.5).
Time Frame	Baseline, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 12 (n=203; n=184)	-6.104 (8.3062)	30.081 (8.7264)
Week 26 (n=207; n=193)	-0.136 (9.7088)	31.669 (10.0562)
Week 42 (n=207; n=193)	-5.571 (7.1395)	16.004 (7.3950)
Week 52 (n=207; n=193)	-9.755 (13.8868)	35.281 (14.3836)

12. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	The change in body weight measured at each week indicated including final visit from baseline.
Time Frame	Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 8 (n=213; n=200)	-0.42 (0.118)	0.55 (0.122)
Week 12 (n=215; n=203)	-0.52 (0.142)	0.42 (0.146)
Week 26 (n=215; n=204)	-0.68 (0.188)	0.66 (0.193)
Week 42 (n=215; n=204)	-0.72 (0.211)	0.57 (0.216)
Week 52 (n=215; n=204)	-0.62 (0.227)	0.60 (0.233)

13. Secondary Outcome

Title	Change From Baseline in Serum Lipids (Total Cholesterol)
Description	The change in total cholesterol measured at each week indicated including final visit from baseline.
Time Frame	Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 8 (n=208; n=195)	-5.6 (2.01)	-1.6 (2.08)
Week 12 (n=213; n=201)	-4.2 (2.06)	-0.7 (2.12)
Week 26 (n=213; n=201)	1.6 (2.03)	0.1 (2.09)
Week 42 (n=213; n=201)	0.2 (2.07)	0.1 (2.13)
Week 52 (n=213; n=201)	-0.8 (2.28)	-0.5 (2.35)

14. Secondary Outcome

Title	Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol)
Description	The change in high-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.
Time Frame	Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 8 (n=206; n=193)	-0.1 (0.59)	1.2 (0.61)
Week 12 (n=212; n=201)	0.4 (0.47)	0.5 (0.48)
Week 26 (n=212; n=201)	1.7 (0.50)	0.2 (0.52)
Week 42 (n=212; n=201)	1.4 (0.59)	0.1 (0.61)
Week 52 (n=212; n=201)	0.8 (0.50)	0.3 (0.51)

15. Secondary Outcome

Title	Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol)
Description	The change in low-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.
Time Frame	Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 8 (n=200; n=185)	-3.2 (1.70)	-2.8 (1.76)
Week 12 (n=208; n=195)	-2.0 (1.75)	-2.4 (1.81)
Week 26 (n=208; n=196)	3.1 (1.67)	-1.1 (1.72)
Week 42 (n=208; n=197)	1.2 (1.79)	-0.8 (1.84)
Week 52 (n=209; n=197)	0.9 (1.83)	-1.4 (1.88)

16. Secondary Outcome

Title	Change From Baseline in Serum Lipids (Triglycerides)
Description	The change in triglycerides measured at each week indicated including final visit from baseline.
Time Frame	Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 8 (n=208; n=195)	-12.8 (5.04)	2.7 (5.20)
Week 12 (n=213; n=201)	-15.5 (5.72)	7.5 (5.89)
Week 26 (n=213; n=201)	-16.3 (4.74)	3.9 (4.88)
Week 42 (n=213; n=201)	-12.6 (5.01)	5.5 (5.16)
Week 52 (n=213; n=201)	-13.2 (5.27)	1.9 (5.42)

17. Secondary Outcome

Title	Change From Baseline in High Sensitivity C-reactive Protein
Description	The change between the high sensitivity C-reactive protein value collected at each week indicated including final visit from baseline.
Time Frame	Baseline, Week 12, Week 26, Week 42 and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Week 12 (n=209; n=192)	0.45 (0.699)	0.10 (0.730)
Week 26 (n=212; n=198)	-0.02 (0.682)	0.47 (0.706)
Week 42 (n=212; n=198)	0.33 (0.736)	0.53 (0.762)
Week 52 (n=212; n=198)	0.01 (0.656)	0.21 (0.679)

18. Secondary Outcome

Title	Incidence of Subjects Achieving Glycosylated Hemoglobin <=7%
Description	The percentage of participants with a value for the percentage of glycosylated hemoglobin (HbA1c; the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5 and 7.0% during the 52 week study.
Time Frame	Baseline and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
HbA1c ≤6.5%	22.3 10%	18.2 8.3%
HbA1c ≤7.0%	48.8 22%	45.3 20.7%

19. Secondary Outcome

Title	Incidence of Glycosylated Hemoglobin Decrease From Baseline.
Description	The percentage of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5, 1.0, 1.5 and 2.0% during the 52 week study.
Time Frame	Baseline and Week 52.

Outcome Measure Data

Analysis Population Description

All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.

Arm/Group Title	Alogliptin 25 mg QD	Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.	Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Measure Participants	222	219
Decrease from Baseline in HbA1c ≥0.5%	32.1 14.5%	29.0 13.2%
Decrease from Baseline in HbA1c ≥1.0%	12.6 5.7%	10.3 4.7%
Decrease from Baseline in HbA1c ≥1.5%	5.1 2.3%	2.3 1.1%
Decrease from Baseline in HbA1c ≥2.0%	2.8 1.3%	1.4 0.6%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug.
Adverse Event Reporting Description	At each visit the investigator was to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Alogliptin 25 mg QD		Glipizide 5 mg QD
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.		Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
All Cause Mortality
	Alogliptin 25 mg QD		Glipizide 5 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alogliptin 25 mg QD		Glipizide 5 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/222 (7.2%)		13/219 (5.9%)
Cardiac disorders
Angina pectoris	1/222 (0.5%)		0/219 (0%)
Cardiac failure	1/222 (0.5%)		0/219 (0%)
Cardiac failure congestive	1/222 (0.5%)		1/219 (0.5%)
Coronary artery disease	1/222 (0.5%)		0/219 (0%)
Ischaemic cardiomyopathy	0/222 (0%)		1/219 (0.5%)
Left ventricular failure	1/222 (0.5%)		0/219 (0%)
Myocardial infarction	0/222 (0%)		1/219 (0.5%)
Ear and labyrinth disorders
Sudden hearing loss	1/222 (0.5%)		0/219 (0%)
Hepatobiliary disorders
Bile duct stone	1/222 (0.5%)		0/219 (0%)
Cholecystitis acute	1/222 (0.5%)		1/219 (0.5%)
Cholelithiasis	0/222 (0%)		2/219 (0.9%)
Infections and infestations
Diverticulitis	1/222 (0.5%)		0/219 (0%)
Pyelonephritis acute	0/222 (0%)		1/219 (0.5%)
Respiratory tract infection viral	0/222 (0%)		1/219 (0.5%)
Urosepsis	0/222 (0%)		1/219 (0.5%)
Injury, poisoning and procedural complications
Fall	2/222 (0.9%)		0/219 (0%)
Graft thrombosis	0/222 (0%)		1/219 (0.5%)
Multiple fractures	1/222 (0.5%)		0/219 (0%)
Postoperative fever	1/222 (0.5%)		0/219 (0%)
Seroma	1/222 (0.5%)		0/219 (0%)
Stress fracture	0/222 (0%)		1/219 (0.5%)
Upper limb fracture	1/222 (0.5%)		0/219 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/222 (0.5%)		0/219 (0%)
Cervix carcinoma	1/222 (0.5%)		0/219 (0%)
Nervous system disorders
Cerebrovascular accident	0/222 (0%)		1/219 (0.5%)
Dizziness	0/222 (0%)		1/219 (0.5%)
Transient ischaemic attack	1/222 (0.5%)		0/219 (0%)
Renal and urinary disorders
Calculus ureteric	1/222 (0.5%)		0/219 (0%)
Renal failure acute	0/222 (0%)		1/219 (0.5%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/222 (0.5%)		0/219 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension	1/222 (0.5%)		0/219 (0%)
Other (Not Including Serious) Adverse Events
	Alogliptin 25 mg QD		Glipizide 5 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	103/222 (46.4%)		105/219 (47.9%)
Gastrointestinal disorders
Diarrhoea	9/222 (4.1%)		14/219 (6.4%)
Dyspepsia	7/222 (3.2%)		1/219 (0.5%)
Nausea	7/222 (3.2%)		8/219 (3.7%)
General disorders
Pyrexia	2/222 (0.9%)		7/219 (3.2%)
Infections and infestations
Bronchitis	6/222 (2.7%)		9/219 (4.1%)
Nasopharyngitis	13/222 (5.9%)		10/219 (4.6%)
Pharyngitis	5/222 (2.3%)		7/219 (3.2%)
Upper respiratory tract infection	12/222 (5.4%)		5/219 (2.3%)
Urinary tract infection	26/222 (11.7%)		23/219 (10.5%)
Investigations
C-reactive protein increased	9/222 (4.1%)		3/219 (1.4%)
Metabolism and nutrition disorders
Dyslipidaemia	5/222 (2.3%)		10/219 (4.6%)
Hypoglycaemia	0/222 (0%)		8/219 (3.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/222 (4.5%)		12/219 (5.5%)
Back pain	9/222 (4.1%)		11/219 (5%)
Osteoarthritis	3/222 (1.4%)		8/219 (3.7%)
Pain in extremity	6/222 (2.7%)		7/219 (3.2%)
Nervous system disorders
Dizziness	13/222 (5.9%)		18/219 (8.2%)
Headache	16/222 (7.2%)		15/219 (6.8%)
Vascular disorders
Hypertension	12/222 (5.4%)		10/219 (4.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.