VITAL: The Effect of Paricalcitol Capsules on Reducing Albuminuria in Patients With Type 2 Diabetic Nephropathy Being Treated With Renin-angiotensin System Inhibitors

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00421733
• Collaborator: (none)
• Enrollment: 281
• Locations: 72
• Arms: 3
• Duration (Months): 30
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study objective was to evaluate the safety of paricalcitol capsules and the efficacy of paricalcitol capsules for albuminuria reduction in patients with Chronic Kidney Disease (CKD) who have Type 2 diabetic nephropathy and are receiving optimal angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II receptor blocker (ARB) therapy.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Nephropathy; Chronic Kidney Disease	Drug: Zemplar (paricalcitol ) capsules; Drug: Zemplar (paricalcitol) capsules; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 281 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: VITAL Study - Selective VITamin D Receptor Activator (Paricalcitol) for Albuminuria Lowering Study: A Phase 2, Prospective, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Paricalcitol Capsules on Reducing Albuminuria in Type 2 Diabetic Nephropathy Subjects Who Are Currently Being Treated With Renin-angiotensin System Inhibitors
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Paricalcitol 1 mcg One paricalcitol 1 mcg capsule and one matching placebo capsule per dose	Drug: Zemplar (paricalcitol ) capsules; Group 2 - paricalcitol 1 mcg capsules once daily (one paricalcitol 1 mcg capsule once daily and one matching placebo capsule once daily); Other Names: ABT-358 paricalcitol Zemplar
Active Comparator: Paricalcitol 2 mcg Two paricalcitol 1 mcg capsules per dose	Drug: Zemplar (paricalcitol) capsules; Group 3 - paricalcitol 2 mcg capsules once daily (two paricalcitol 1 mcg capsules once daily); Other Names: ABT-358 paricalcitol Zemplar
Placebo Comparator: Placebo Two placebo capsules per dose	Drug: Placebo; Group 1 - Placebo once daily (two placebo capsules once daily)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to the Last On-treatment Measurement in Urine Albumin to Creatinine Ratio (UACR) Levels Determined From the First Morning Void (FMV) Urine Collections Comparing Placebo to the Combined Paricalcitol Treatment Groups (1 Mcg and 2 Mcg). [Baseline (within 1 week prior to first treatment) through 24 weeks of treatment]

   UACR is defined as the ratio: milligram of albumin per gram of creatinine. Baseline UACR was determined as the mean of the 3 UACR measurements from FMV urine collections obtained within 1 week prior to the day of the first dose of study drug. The last on-treatment measurement was the mean of the 3 UACR measurements obtained from FMV urine collections obtained within 1 week of the final week of treatment. The UACR data were log transformed prior to analysis.

Secondary Outcome Measures

1. Number of Participants Achieving a 15% or Greater Reduction From Baseline to Last On-treatment Urine Albumin to Creatinine Ratio (UACR) Levels. [Baseline (within 1 week prior to first treatment) through 24 weeks of treatment]

   Number of participants whose last on-treatment albumin to creatinine ratio (UACR) value was reduced at least 15% from the baseline value. Albumin values were determined from 24-hour urine collections from the baseline and last on-treatment visits.

2. Change From Baseline to the Last On-treatment Measurement in Albumin Levels Determined From 24-hour Urine Collection. [Baseline (within 1 week prior to first treatment) through 24 weeks of treatment]

   The change is mean change from baseline to the last on-treatment value, with the data being log transformed prior to analysis. Albumin values were determined from 24-hour urine collections from the baseline and last on-treatment visits.

3. Change From Baseline to the Last On-treatment Observation in Intact Parathyroid Hormone (iPTH) Levels. [Baseline (screening period) through 24 weeks of treatment]

   Change is mean change in picograms of iPTH per milliliter of serum.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female participant >= 20 years old.

• Participant has Type 2 Diabetes Mellitus and has been treated with at least one anti-hyperglycemic medication within the 12 months prior to the Screening Phase

• Participant has been receiving a stable dose (i.e., same type and regimen) of ACEi and/or ARB for at least three months prior to the Screening Phase. However, participant may have switched to different brands but at equivalent doses during the three months prior to the Screening Phase.

• Participant is not expected to begin dialysis for at least 6 months.

• If female, participant is not breast feeding or is not pregnant.

• For entry into the Treatment Phase, the participant must satisfy the following criteria based on the Screening laboratory values:

• Estimated glomerular filtration rate (GFR) between 15-90 mL/min/1.73m2 by simplified Modification in Diet in Renal Disease (MDRD) formula

• Urinary albumin to creatinine ratio (UACR) between 100 and 3000 mg/g as determined by the mean of the three first morning void urine specimens obtained within one week of each other

• Corrected serum calcium level <= 9.8 mg/dL

• intact parathyroid hormone (iPTH) value between 35-500 pg/mL

• Glycosylated hemoglobin A1c (HbA1c) <= 12%

• Serum albumin > 3.0 g/dL

• Negative urine pregnancy test for female participants

Exclusion Criteria:

• Participant has previously been on prescription-based vitamin D therapy within the six months prior to the Screening Phase.

• Participant has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug.

• Participant has primary glomerulonephritis or secondary nephritis in addition to diabetic nephropathy.

• Participant has had acute renal failure within 12 weeks of the Screening Phase, defined as an acute rise (of >= 0.5 mg/dL) in serum creatinine to > 4 mg/dL.

• Participant has chronic gastrointestinal disease.

• Participant has secondary hypertension.

• Participant has poorly controlled hypertension.

• Participant has a history of kidney stones.

• Participant has a history of drug or alcohol abuse within six months prior to the Screening Phase.

• Participant has evidence of poor compliance with diet or medication.

• Participant has received any investigational drug within 30 days prior to study drug administration.

• Participant is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical glucocorticoids), or other drugs that may affect calcium, or bone metabolism, other than calcium containing phosphate binder or female participants on stable (same dose and product for three months) estrogen and/or progestin therapy.

• For any reason, participant is considered by the Investigator to be an unsuitable candidate to receive paricalcitol capsules or is put at risk by study procedures.

• Participant is known to be human immunodeficiency virus (HIV) positive.

• Participant has used known inhibitors or inducers of cytochrome P450 3A (CYP3A) within two weeks prior to study drug administration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 862	Phoenix	Arizona	United States	85012
2	Site Reference ID/Investigator# 864	Fountain Valley	California	United States	92708
3	Site Reference ID/Investigator# 7291	Yuba City	California	United States	95991
4	Site Reference ID/Investigator# 853	Hudson	Florida	United States	34667
5	Site Reference ID/Investigator# 867	Lauderdale Lakes	Florida	United States	33313
6	Site Reference ID/Investigator# 857	Pembroke Pines	Florida	United States	33028
7	Site Reference ID/Investigator# 8901	West Palm Beach	Florida	United States	33401
8	Site Reference ID/Investigator# 7113	Roswell	Georgia	United States	30076
9	Site Reference ID/Investigator# 2531	Chicago	Illinois	United States	60654
10	Site Reference ID/Investigator# 3371	Evanston	Illinois	United States	60201
11	Site Reference ID/Investigator# 869	Indianapolis	Indiana	United States	46202
12	Site Reference ID/Investigator# 8054	Baton Rouge	Louisiana	United States	70808
13	Site Reference ID/Investigator# 854	Rockville	Maryland	United States	20852
14	Site Reference ID/Investigator# 6281	Boston	Massachusetts	United States	02215
15	Site Reference ID/Investigator# 859	Brooklyn Center	Minnesota	United States	55430
16	Site Reference ID/Investigator# 7214	Omaha	Nebraska	United States	68131
17	Site Reference ID/Investigator# 8046	Albany	New York	United States	12206
18	Site Reference ID/Investigator# 866	Charlotte	North Carolina	United States	28208
19	Site Reference ID/Investigator# 8039	Greenville	North Carolina	United States	27834
20	Site Reference ID/Investigator# 8053	Morehead City	North Carolina	United States	28557
21	Site Reference ID/Investigator# 6626	Winston-Salem	North Carolina	United States	27103
22	Site Reference ID/Investigator# 7495	Carlisle	Pennsylvania	United States	17015
23	Site Reference ID/Investigator# 9061	Dallas	Texas	United States	75230
24	Site Reference ID/Investigator# 8325	Dallas	Texas	United States	75231
25	Site Reference ID/Investigator# 856	Dallas	Texas	United States	75390
26	Site Reference ID/Investigator# 7494	San Antonio	Texas	United States	78229
27	Site Reference ID/Investigator# 774	San Antonio	Texas	United States	78229
28	Site Reference ID/Investigator# 6316	Duesseldorf		Germany	40210
29	Site Reference ID/Investigator# 5167	Hannover		Germany	30625
30	Site Reference ID/Investigator# 6302	Ludwigshafen		Germany	67059
31	Site Reference ID/Investigator# 6314	Athens		Greece	18454
32	Site Reference ID/Investigator# 6306	Ioannina		Greece	45500
33	Site Reference ID/Investigator# 5631	Thessaloniki		Greece	54636
34	Site Reference ID/Investigator# 6310	Thessaloniki		Greece	54642
35	Site Reference ID/Investigator# 6312	Bergamo		Italy	24128
36	Site Reference ID/Investigator# 6303	Brescia		Italy	25123
37	Site Reference ID/Investigator# 6309	Milan		Italy	20142
38	Site Reference ID/Investigator# 6210	Modena		Italy	41100
39	Site Reference ID/Investigator# 6207	Groningen		Netherlands	9713 GZ
40	Site Reference ID/Investigator# 6304	Bydgoszcz		Poland	85-094
41	Site Reference ID/Investigator# 5622	Katowice		Poland	40027
42	Site Reference ID/Investigator# 5203	Szczecin		Poland	70-111
43	Site Reference ID/Investigator# 6315	Warsaw		Poland	00909
44	Site Reference ID/Investigator# 6327	Lisbon		Portugal	1069-166
45	Site Reference ID/Investigator# 6326	Porto		Portugal	4202-451
46	Site Reference ID/Investigator# 6916	Caguas		Puerto Rico	00725
47	Site Reference ID/Investigator# 5175	Carolina		Puerto Rico	00983
48	Site Reference ID/Investigator# 6290	Las Piedras		Puerto Rico	00771
49	Site Reference ID/Investigator# 5179	Ponce		Puerto Rico	00716
50	Site Reference ID/Investigator# 6293	Ponce		Puerto Rico	00716
51	Site Reference ID/Investigator# 5173	Ponce		Puerto Rico	00717-0634
52	Site Reference ID/Investigator# 6300	Ponce		Puerto Rico	00717-1322
53	Site Reference ID/Investigator# 5168	Ponce		Puerto Rico	00717-2075
54	Site Reference ID/Investigator# 7298	Rio Piedras		Puerto Rico	00935
55	Site Reference ID/Investigator# 5170	San Juan		Puerto Rico	00909
56	Site Reference ID/Investigator# 7509	San Juan		Puerto Rico	00918
57	Site Reference ID/Investigator# 6288	San Juan		Puerto Rico	00921-3201
58	Site Reference ID/Investigator# 6291	San Juan		Puerto Rico	00936-5067
59	Site Reference ID/Investigator# 6919	Toa Baja		Puerto Rico	00949
60	Site Reference ID/Investigator# 6296	Yabucoa		Puerto Rico	00767
61	Site Reference ID/Investigator# 6569	Barcelona		Spain	08036
62	Site Reference ID/Investigator# 10621	Galdakao		Spain	48960
63	Site Reference ID/Investigator# 6330	L'Hospitalet de		Spain	08907
64	Site Reference ID/Investigator# 5111	Madrid		Spain	28041
65	Site Reference ID/Investigator# 5110	Oviedo		Spain	33006
66	Site Reference ID/Investigator# 6329	Santander		Spain	39008
67	Site Reference ID/Investigator# 11281	Valencia		Spain	46017
68	Site Reference ID/Investigator# 6286	Hsin-Chuang City		Taiwan
69	Site Reference ID/Investigator# 8335	Taichung City		Taiwan	40764
70	Site Reference ID/Investigator# 7927	Taichung		Taiwan	433
71	Site Reference ID/Investigator# 6294	Taipei City		Taiwan	10449
72	Site Reference ID/Investigator# 6285	Taipei		Taiwan

Sponsors and Collaborators

• Abbott

Investigators

• Study Director: Dennis Andress, MD, Abbott

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00421733
• Other Study ID Numbers: M05-741; 2006-001363-31
• First Posted: Jan 12, 2007
• Last Update Posted: Jan 20, 2012
• Last Verified: Jan 1, 2012

• Keywords provided by Abbott: Type 2 Diabetic Nephropathy
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Albuminuria; Ergocalciferols

Study Results

Participant Flow

Arm/Group Title	Paricalcitol 1 Mcg	Paricalcitol 2 Mcg	Placebo
Arm/Group Description	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose	Two paricalcitol 1 mcg capsules per dose	Two placebo capsules per dose
Period Title: Overall Study
STARTED	93	95	93
COMPLETED	78	69	73
NOT COMPLETED	15	26	20

Baseline Characteristics

Arm/Group Title	Paricalcitol 1 Mcg	Paricalcitol 2 Mcg	Placebo	Total
Arm/Group Description	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose	Two paricalcitol 1 mcg capsules per dose	Two placebo capsules per dose	Total of all reporting groups
Overall Participants	93	95	93	281
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	45 48.4%	47 49.5%	44 47.3%	136 48.4%
>=65 years	48 51.6%	48 50.5%	49 52.7%	145 51.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (10.15)	64.7 (9.92)	64.5 (11.23)	64.4 (10.41)
Sex: Female, Male (Count of Participants)
Female	27 29%	26 27.4%	33 35.5%	86 30.6%
Male	66 71%	69 72.6%	60 64.5%	195 69.4%
Region of Enrollment (participants) [Number]
Portugal	2 2.2%	2 2.1%	0 0%	4 1.4%
United States	57 61.3%	60 63.2%	64 68.8%	181 64.4%
Taiwan	10 10.8%	14 14.7%	10 10.8%	34 12.1%
Greece	1 1.1%	3 3.2%	1 1.1%	5 1.8%
Poland	4 4.3%	4 4.2%	4 4.3%	12 4.3%
Spain	11 11.8%	3 3.2%	9 9.7%	23 8.2%
Netherlands	0 0%	0 0%	1 1.1%	1 0.4%
Germany	4 4.3%	8 8.4%	1 1.1%	13 4.6%
Italy	4 4.3%	1 1.1%	3 3.2%	8 2.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to the Last On-treatment Measurement in Urine Albumin to Creatinine Ratio (UACR) Levels Determined From the First Morning Void (FMV) Urine Collections Comparing Placebo to the Combined Paricalcitol Treatment Groups (1 Mcg and 2 Mcg).
Description	UACR is defined as the ratio: milligram of albumin per gram of creatinine. Baseline UACR was determined as the mean of the 3 UACR measurements from FMV urine collections obtained within 1 week prior to the day of the first dose of study drug. The last on-treatment measurement was the mean of the 3 UACR measurements obtained from FMV urine collections obtained within 1 week of the final week of treatment. The UACR data were log transformed prior to analysis.
Time Frame	Baseline (within 1 week prior to first treatment) through 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat population, which was all randomized participants who received at least 1 dose of study drug. Subjects without both a baseline and last on-treatment measurement were excluded from the primary efficacy analysis. As such, sample size was N=88 for placebo, N=92 for 1 mcg and for 2 mcg paricalcitol, and N=184 for combined paricalcitol.

Arm/Group Title	Placebo	Combined Paricalcitol 1 Mcg and 2 Mcg	Paricalcitol 1 Mcg	Paricalcitol 2 Mcg
Arm/Group Description	Two placebo capsules per dose (N=88)	Combined participants in the 1 mcg and 2 mcg paricalcitol groups (N=92+92=184).	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose	Two paricalcitol 1 mcg capsules per dose
Measure Participants	88	184	92	92
Mean (Standard Deviation) [log milligram/gram creatinine]	-0.03 (0.61)	-0.18 (0.70)	-0.15 (0.72)	-0.22 (0.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Combined Paricalcitol 1 Mcg and 2 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.071
	Comments	There were no P-value adjustments for multiple comparisons.
	Method	ANCOVA
	Comments	1-way ANCOVA using treatment group as the factor and baseline FMV UACR as the covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paricalcitol 1 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.229
	Comments	There were no P-value adjustments for multiple comparisons.
	Method	ANCOVA
	Comments	1-way ANCOVA with treatment group as the factor and baseline FMV UACR as the covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paricalcitol 2 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments	There were no P-value adjustments for multiple comparisons.
	Method	ANCOVA
	Comments	1-way ANCOVA using treatment group as the factor and baseline FMV UACR as the covariate.

2. Secondary Outcome

Title	Number of Participants Achieving a 15% or Greater Reduction From Baseline to Last On-treatment Urine Albumin to Creatinine Ratio (UACR) Levels.
Description	Number of participants whose last on-treatment albumin to creatinine ratio (UACR) value was reduced at least 15% from the baseline value. Albumin values were determined from 24-hour urine collections from the baseline and last on-treatment visits.
Time Frame	Baseline (within 1 week prior to first treatment) through 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat population, which was all randomized subjects who received at least one dose of study drug. Subjects who did not have both a baseline measurement and a last on-treatment visit value were excluded from the analyses.

Arm/Group Title	Paricalcitol 1 Mcg	Paricalcitol 2 Mcg	Placebo
Arm/Group Description	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose	Two paricalcitol 1 mcg capsules per dose	Two placebo capsules per dose
Measure Participants	92	92	88
Number [Participants]	48 51.6%	51 53.7%	35 37.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paricalcitol 1 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.102
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combined Paricalcitol 1 Mcg and 2 Mcg, Paricalcitol 1 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Change From Baseline to the Last On-treatment Measurement in Albumin Levels Determined From 24-hour Urine Collection.
Description	The change is mean change from baseline to the last on-treatment value, with the data being log transformed prior to analysis. Albumin values were determined from 24-hour urine collections from the baseline and last on-treatment visits.
Time Frame	Baseline (within 1 week prior to first treatment) through 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat population, which was all randomized subjects who received at least one dose of study drug. Subjects who did not have both a baseline measurement and a last on-treatment visit value were excluded from the analyses.

Arm/Group Title	Paricalcitol 1 Mcg	Paricalcitol 2 Mcg	Placebo
Arm/Group Description	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose	Two paricalcitol 1 mcg capsules per dose	Two placebo capsules per dose
Measure Participants	74	72	78
Mean (Standard Deviation) [log milligrams of albumin per 24 hours]	-0.10 (0.73)	-0.44 (0.90)	-0.08 (0.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paricalcitol 1 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.855
	Comments
	Method	ANCOVA
	Comments	2-way ANCOVA: baseline UACR as covariate; fixed factors for treatment group, stratification level, and treatment by stratification level interaction
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combined Paricalcitol 1 Mcg and 2 Mcg, Paricalcitol 1 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANCOVA
	Comments	2-way ANCOVA: baseline UACR as covariate; fixed factors for treatment group, stratification level, and treatment by stratification level interaction
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.57 to -0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to the Last On-treatment Observation in Intact Parathyroid Hormone (iPTH) Levels.
Description	Change is mean change in picograms of iPTH per milliliter of serum.
Time Frame	Baseline (screening period) through 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat population, which was all randomized subjects who received at least one dose of study drug. Subjects who did not have both a baseline and a last on-treatment measurement were excluded from the analyses.

Arm/Group Title	Paricalcitol 1 Mcg	Paricalcitol 2 Mcg	Placebo
Arm/Group Description	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose	Two paricalcitol 1 mcg capsules per dose	Two placebo capsules per dose
Measure Participants	92	90	88
Mean (Standard Deviation) [picogram/milliliter]	-26.7 (55.2)	-50.7 (63.1)	18.3 (55.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paricalcitol 1 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	1-way ANCOVA with treatment group as the factor and baseline iPTH as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combined Paricalcitol 1 Mcg and 2 Mcg, Paricalcitol 1 Mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	1-way ANCOVA with treatment group as the factor and baseline iPTH as covariate.

Adverse Events

Time Frame	up to 24 weeks
Adverse Event Reporting Description	Treatment-emergent serious adverse and non-serious adverse events were reported after the first dose of study drug through 30 days after the last dose of study drug.
Arm/Group Title	Paricalcitol 1 Mcg		Paricalcitol 2 Mcg		Placebo
Arm/Group Description	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose		Two paricalcitol 1 mcg capsules per dose		Two placebo capsules per dose
All Cause Mortality
	Paricalcitol 1 Mcg		Paricalcitol 2 Mcg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Paricalcitol 1 Mcg		Paricalcitol 2 Mcg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/93 (14%)		19/95 (20%)		12/93 (12.9%)
Blood and lymphatic system disorders
Anaemia	0/93 (0%)		1/95 (1.1%)		1/93 (1.1%)
Thrombocytopenia	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Cardiac disorders
Acute myocardial infarction	0/93 (0%)		2/95 (2.1%)		0/93 (0%)
Angina pectoris	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Atrial flutter	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Bradycardia	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Cardiac failure congestive	0/93 (0%)		1/95 (1.1%)		1/93 (1.1%)
Cardio-respiratory arrest	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Coronary artery disease	1/93 (1.1%)		1/95 (1.1%)		0/93 (0%)
Intracardiac thrombus	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Ventricular tachycardia	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Congenital, familial and genetic disorders
Gastrointestinal angiodysplasia haemorrhagic	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Eye disorders
Cataract	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Retinal oedema	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Gastrointestinal disorders
Duodenitis	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Gastritis	0/93 (0%)		0/95 (0%)		2/93 (2.2%)
Gastrointestinal haemorrhage	0/93 (0%)		1/95 (1.1%)		1/93 (1.1%)
Inguinal hernia	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Rectal haemorrhage	0/93 (0%)		1/95 (1.1%)		1/93 (1.1%)
General disorders
Asthenia	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Chest pain	1/93 (1.1%)		1/95 (1.1%)		0/93 (0%)
Death	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Impaired healing	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Non-cardiac chest pain	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Oedema peripheral	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Infections and infestations
Bacteraemia	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Cellulitis	0/93 (0%)		1/95 (1.1%)		1/93 (1.1%)
Pneumonia	1/93 (1.1%)		1/95 (1.1%)		0/93 (0%)
Posteroperative wound infection	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Respiratory tract infection	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Sepsis	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Investigations
Blood pressure increased	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Fluid overload	0/93 (0%)		2/95 (2.1%)		0/93 (0%)
Hypoglycaemia	2/93 (2.2%)		0/95 (0%)		0/93 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign colonic neoplasm	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Colon cancer	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Oesophageal cancer	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Nervous system disorders
Cerebrovascular accident	0/93 (0%)		2/95 (2.1%)		0/93 (0%)
Dizziness	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Psychiatric disorders
Nervousness	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Substance abuse	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Renal and urinary disorders
Renal failure	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Renal failure acute	1/93 (1.1%)		2/95 (2.1%)		1/93 (1.1%)
Renal failure chronic	0/93 (0%)		1/95 (1.1%)		1/93 (1.1%)
Renal impairment	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/93 (0%)		1/95 (1.1%)		1/93 (1.1%)
Dyspnoea exertional	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Respiratory failure	0/93 (0%)		1/95 (1.1%)		0/93 (0%)
Vascular disorders
Extremity necrosis	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Hypertensive crisis	1/93 (1.1%)		0/95 (0%)		0/93 (0%)
Hypotension	0/93 (0%)		2/95 (2.1%)		0/93 (0%)
Thrombosis	0/93 (0%)		0/95 (0%)		1/93 (1.1%)
Other (Not Including Serious) Adverse Events
	Paricalcitol 1 Mcg		Paricalcitol 2 Mcg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/93 (40.9%)		46/95 (48.4%)		46/93 (49.5%)
Blood and lymphatic system disorders
Anemia	5/93 (5.4%)		8/95 (8.4%)		5/93 (5.4%)
Gastrointestinal disorders
Constipation	3/93 (3.2%)		2/95 (2.1%)		1/93 (1.1%)
Diarrhoea	3/93 (3.2%)		1/95 (1.1%)		6/93 (6.5%)
Nausea	2/93 (2.2%)		2/95 (2.1%)		4/93 (4.3%)
General disorders
Chest pain	0/93 (0%)		0/95 (0%)		3/93 (3.2%)
Fatigue	1/93 (1.1%)		5/95 (5.3%)		1/93 (1.1%)
Oedema	3/93 (3.2%)		3/95 (3.2%)		1/93 (1.1%)
Oedema peripheral	5/93 (5.4%)		4/95 (4.2%)		4/93 (4.3%)
Pyrexia	0/93 (0%)		0/95 (0%)		3/93 (3.2%)
Infections and infestations
Bronchitis	3/93 (3.2%)		2/95 (2.1%)		1/93 (1.1%)
Nasopharyngitis	2/93 (2.2%)		3/95 (3.2%)		2/93 (2.2%)
Tinea pedis	0/93 (0%)		0/95 (0%)		3/93 (3.2%)
Upper respiratory tract infection	5/93 (5.4%)		5/95 (5.3%)		4/93 (4.3%)
Urinary tract infection	2/93 (2.2%)		6/95 (6.3%)		2/93 (2.2%)
Investigations
Blood parathyroid hormone decreased	2/93 (2.2%)		3/95 (3.2%)		0/93 (0%)
Metabolism and nutrition disorders
Gout	1/93 (1.1%)		1/95 (1.1%)		3/93 (3.2%)
Hyperglycaemia	0/93 (0%)		2/95 (2.1%)		3/93 (3.2%)
Hyperkalaemia	3/93 (3.2%)		5/95 (5.3%)		4/93 (4.3%)
Hypoglycaemia	2/93 (2.2%)		3/95 (3.2%)		4/93 (4.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/93 (1.1%)		4/95 (4.2%)		2/93 (2.2%)
Muscle spasms	0/93 (0%)		1/95 (1.1%)		5/93 (5.4%)
Osteoarthritis	2/93 (2.2%)		3/95 (3.2%)		0/93 (0%)
Pain in extremity	4/93 (4.3%)		2/95 (2.1%)		3/93 (3.2%)
Nervous system disorders
Dizziness	3/93 (3.2%)		3/95 (3.2%)		1/93 (1.1%)
Headache	0/93 (0%)		3/95 (3.2%)		4/93 (4.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonsry disease	0/93 (0%)		3/95 (3.2%)		0/93 (0%)
Cough	5/93 (5.4%)		0/95 (0%)		3/93 (3.2%)
Vascular disorders
Hypertension	5/93 (5.4%)		8/95 (8.4%)		11/93 (11.8%)

Limitations/Caveats

[Not Specified]

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

Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.