Extension Study of CTAP101-CL-3001 or CTAP101-CL-3002

• Sponsor: OPKO Health, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02282813
• Collaborator: (none)
• Enrollment: 298
• Arms: 4
• Duration (Months): 25

Study Details

Study Description

Brief Summary

This extension study of subjects previously enrolled in studies CTAP101-CL-3001 or CTAP101-CL-3002 allows long term evaluation of the safety and efficacy of CTAP101 Capsules in reducing elevated intact parathyroid hormone (iPTH) and correcting vitamin D insufficiency in stage 3 or 4 chronic kidney disease patients.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease; Hyperparathyroidism, Secondary; Vitamin D Deficiency	Drug: CTAP101 Capsules; Drug: Calcitriol; Drug: Doxercalciferol; Drug: Paricalcitol	Phase 3

Detailed Description

Only subjects previously enrolled in studies CTAP101-CL-3001 or CTAP101-CL-3002 are eligible to participate in this extension study. This is a phase 3, open-label study of CTAP101 Capsules, with and without add-on vitamin D hormone therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 298 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-term Safety and Efficacy Study of CTAP101 Capsules in Subjects With Stages 3 or 4 Chronic Kidney Disease, Secondary Hyperparathyroidism and Vitamin D Insufficiency (Extension of Study CTAP101-CL-3001 or CTAP101-CL-3002)
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CTAP101 Capsules alone CTAP101 Capsules 30 or 60 mcg daily for up to 26 weeks	Drug: CTAP101 Capsules; At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily; Other Names: Calcifediol
Experimental: CTAP101 Capsules +calcitriol CTAP101 Capsules 60 mcg +calcitriol daily for 14 weeks	Drug: CTAP101 Capsules; At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily; Other Names: Calcifediol ; Drug: Calcitriol; At week 12, eligible subjects will be randomized to also take calcitriol 0.25 mcg dose one capsule daily; Other Names: calcifediol
Experimental: CTAP101 Capsules +doxercalciferol CTAP101 Capsules 60 mcg +doxercalciferol daily for 14 weeks	Drug: CTAP101 Capsules; At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily; Other Names: Calcifediol ; Drug: Doxercalciferol; At week 12, eligible subjects will be randomized to also take doxercalciferol 0.5 mcg one capsule daily; Other Names: calcifediol
Experimental: CTAP101 Capsules +paricalcitol CTAP101 Capsules 60 mcg +paricalcitol daily for 14 weeks	Drug: CTAP101 Capsules; At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily; Other Names: Calcifediol ; Drug: Paricalcitol; At week 12, eligible subjects will be randomized to also take paricalcitol 1 mcg one capsule daily; Other Names: calcifediol

Outcome Measures

Primary Outcome Measures

1. Number of Participants in the Intent to Treat Population With a Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) [up to 6 months]

   Number of subjects in the intent to treat population with a mean reduction in plasma intact parathyroid hormone (iPTH) of >/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders

Secondary Outcome Measures

1. Number of Participants in the Per Protocol Population With Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) [up to 6 months]

   Number of subjects in the per protocol population with a mean reduction in plasma intact parathyroid hormone (iPTH) of >/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders

2. Number of Participants in the Intent to Treat Population With Normal Serum 25-hydroxyvitamin D at End of Treatment (EOT) [up to 6 months]

   Number of Participants in the Intent to Treat Population with serum 25-hydroxyvitamin D >/= 30 ng/mL at End of Treatment (EOT)

3. Number of Participants in the Per Protocol Population With NormalSerum 25-hydroxyvitamin D at End of Treatment (EOT) [up to 6 months]

   Number of Participants in the per protocol population with serum 25-hydroxyvitamin D >/= 30 ng/mL at End of Treatment (EOT)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completed either of the phase 3 double-blind, placebo-controlled studies, CTAP101-CL-3001 or CTAP101-CL-3002

• Taking no more than 1000 mg/day of elemental Ca and willing/able to remain on this dose for the duration of the study

• Taking no more than 1600 IU/dose vitamin D (ergocalciferol or cholecalciferol) therapy and willing/able to remain on a stable dose of vitamin D during the study

• Willing and able to comply with study instructions and to commit to all clinic visits for the duration of the study

• Female subjects of childbearing potential must be neither pregnant nor lactating and must have a negative urine pregnancy test

• All female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception (eg, implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence, vasectomy or vasectomized partner) for the duration of the study

• Have the ability to read and understand subject Informed Consent Form (ICF). Subjects or their legal representatives must sign the ICF.

Exclusion Criteria:

• Use of pharmacological dose of ergocalciferol and cholecalciferol (monthly equivalent of 50,000 IU or 1250 µg, eg, Drisdol®) or bisphosphonate therapy

• Use of other bone metabolism therapy (with the exception of stable doses of bisphosphonates and denosumab [Xgeva® and Prolia®]) that may interfere with study endpoints

• Concomitant serious illness or medical condition, such as malignancy, human immunodeficiency virus, significant gastrointestinal or hepatic disease or cardiovascular event or hepatitis that in the opinion of the investigator may worsen and/or interfere with participation in the study

• Neurological/psychiatric disorder, including psychotic disorder or dementia, or any condition reason which, in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely

• Known or suspected hypersensitivity to any of the constituents of either investigational product (CTAP101) or adjunctive vitamin D hormone therapy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• OPKO Health, Inc.

Investigators

• Study Director: Joel Melnick, MD, OPKO Renal

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: OPKO Health, Inc.
• ClinicalTrials.gov Identifier: NCT02282813
• Other Study ID Numbers: CTAP101-CL-3003
• First Posted: Nov 4, 2014
• Last Update Posted: Sep 29, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by OPKO Health, Inc.: Parathyroid Diseases; Renal Insufficiency; Kidney Failure, Chronic; Hyperparathyroidism, Secondary; Vitamin D; Hyperparathyroidism; Kidney Diseases; Kidney Failure; Renal Insufficiency, Chronic
• Additional relevant MeSH terms: Neoplasm Metastasis; Kidney Diseases; Renal Insufficiency, Chronic; Vitamin D Deficiency; Hyperparathyroidism; Hyperparathyroidism, Secondary; Calcitriol; Calcifediol; 1 alpha-hydroxyergocalciferol

Study Results

Participant Flow

Recruitment Details	Subjects could enroll in extension study after completing trials CTAP101-CL-3001 or CTAP101-CL-3002. Subjects from 68 sites participated with at least 1 subject enrolled in the extension per site. Three sites participated in both blinded trials.
Pre-assignment Detail	Treatment groups were categorized as treated for 26 weeks; subjects previously on placebo in predecessor trials) or 12 months (52 weeks; subjects previously on active treatment in predecessor trials). Following 12 weeks, a subset of eligible subjects (n=up to 90) could be randomized to take adjunctive therapy in addition to CTAP101 capsules.

Arm/Group Title	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)	CTAP101 Capsules (Not Randomized; 12 Mos Treatment)	CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
Arm/Group Description	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily.	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily	CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules.
Period Title: Overall Study
STARTED	103	153	42
COMPLETED	91	130	39
NOT COMPLETED	12	23	3

Baseline Characteristics

Arm/Group Title	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)	CTAP101 Capsules (Monotherapy; 12 Mos Treatment)	CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive	Total
Arm/Group Description	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily.	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily	CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules.	Total of all reporting groups
Overall Participants	103	153	42	298
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.7 (10.78)	66.9 (9.83)	65.0 (12.34)	65.9 (10.56)
Sex: Female, Male (Count of Participants)
Female	55 53.4%	85 55.6%	14 33.3%	154 51.7%
Male	48 46.6%	68 44.4%	28 66.7%	144 48.3%
Region of Enrollment (participants) [Number]
United States	103 100%	153 100%	42 100%	298 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants in the Intent to Treat Population With a Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT)
Description	Number of subjects in the intent to treat population with a mean reduction in plasma intact parathyroid hormone (iPTH) of >/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders
Time Frame	up to 6 months

Outcome Measure Data

Analysis Population Description

Intent to treat

Arm/Group Title	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)	CTAP101 Capsules (Not Randomized; 12 Mos Treatment)	CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
Arm/Group Description	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects continued to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily.	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects continued to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily	CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules.
Measure Participants	103	153	42
Number [participants]	34 33%	66 43.1%	30 71.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CTAP101 Capsules (Not Randomized; 6 Mos Treatment), CTAP101 Capsules (Not Randomized; 12 Mos Treatment)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1041
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Number of Participants in the Per Protocol Population With Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT)
Description	Number of subjects in the per protocol population with a mean reduction in plasma intact parathyroid hormone (iPTH) of >/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders
Time Frame	up to 6 months

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)	CTAP101 Capsules (Not Randomized; 12 Mos Treatment)	CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
Arm/Group Description	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily.	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily	CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules.
Measure Participants	91	126	40
Number [participants]	34 33%	64 41.8%	29 69%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CTAP101 Capsules (Not Randomized; 6 Mos Treatment), CTAP101 Capsules (Not Randomized; 12 Mos Treatment)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.0503
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Number of Participants in the Intent to Treat Population With Normal Serum 25-hydroxyvitamin D at End of Treatment (EOT)
Description	Number of Participants in the Intent to Treat Population with serum 25-hydroxyvitamin D >/= 30 ng/mL at End of Treatment (EOT)
Time Frame	up to 6 months

Outcome Measure Data

Analysis Population Description

Intent to treat

Arm/Group Title	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)	CTAP101 Capsules (Not Randomized; 12 Mos Treatment)	CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
Arm/Group Description	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily.	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily	CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules.
Measure Participants	103	153	42
Number [participants]	87 84.5%	124 81%	38 90.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CTAP101 Capsules (Not Randomized; 6 Mos Treatment), CTAP101 Capsules (Not Randomized; 12 Mos Treatment)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4817
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Number of Participants in the Per Protocol Population With NormalSerum 25-hydroxyvitamin D at End of Treatment (EOT)
Description	Number of Participants in the per protocol population with serum 25-hydroxyvitamin D >/= 30 ng/mL at End of Treatment (EOT)
Time Frame	up to 6 months

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)	CTAP101 Capsules (Not Randomized; 12 Mos Treatment)	CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
Arm/Group Description	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily.	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily	CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules.
Measure Participants	91	126	40
Number [participants]	86 83.5%	120 78.4%	37 88.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CTAP101 Capsules (Not Randomized; 6 Mos Treatment), CTAP101 Capsules (Not Randomized; 12 Mos Treatment)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8086
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	6 months from initiation of treatment through end of treatment
Arm/Group Title	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)		CTAP101 Capsules (Not Randomized; 12 Mos Treatment)		CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
Arm/Group Description	CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily.		CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26. CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily		CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules.
All Cause Mortality
	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)		CTAP101 Capsules (Not Randomized; 12 Mos Treatment)		CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)		CTAP101 Capsules (Not Randomized; 12 Mos Treatment)		CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/103 (17.5%)		33/153 (21.6%)		9/42 (21.4%)
Blood and lymphatic system disorders
Anaemia	0/103 (0%)	0	2/153 (1.3%)	2	0/42 (0%)	0
Cardiac disorders
Cardiac failure congestive	3/103 (2.9%)	3	2/153 (1.3%)	2	1/42 (2.4%)	1
Acute myocardial infarction	1/103 (1%)	1	2/153 (1.3%)	2	0/42 (0%)	0
Cardiac arrest	1/103 (1%)	1	2/153 (1.3%)	2	0/42 (0%)	0
Angina pectoris	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Bradycardia	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Cardiac failure chronic	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Coronary artery disease	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Myocardial infarction	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Sick sinus syndrome	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Duodenitis	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Haematochezia	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Diarrhoea	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
Upper gastrointestinal haemorrhage	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
General disorders
Chest pain	0/103 (0%)	0	2/153 (1.3%)	2	0/42 (0%)	0
Asthenia	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Hepatobiliary disorders
Hepatic cirrhosis	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Infections and infestations
Pneumonia	1/103 (1%)	1	3/153 (2%)	3	0/42 (0%)	0
Cellulitis	1/103 (1%)	1	2/153 (1.3%)	2	1/42 (2.4%)	1
Sepsis	2/103 (1.9%)	2	1/153 (0.7%)	1	0/42 (0%)	0
Urinary tract infection	1/103 (1%)	1	2/153 (1.3%)	2	1/42 (2.4%)	1
Bronchitis	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Enterococcal	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Eschericia infection	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Eschericia sepsis	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Gastroenteritis	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Septic shock	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Sinusitis	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Wound infection	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Injury, poisoning and procedural complications
Patella fracture	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Tibia	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Investigations
Blood creatinine increased	0/103 (0%)	0	2/153 (1.3%)	2	0/42 (0%)	0
Blood creatinine phosphokinase MB increased	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/103 (1%)	1	1/153 (0.7%)	1	0/42 (0%)	0
Decreased appetite	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Dehydration	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Diabetes with hyperosmolarity	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Fluid overload	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Hyperglycaemia	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
Hypoglycaemia	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Gouty arthritis	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Lumbar spinal stenosis	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Osteoarthritis	0/103 (0%)	0	1/153 (0.7%)	1	1/42 (2.4%)	1
Pain in extremity	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Rotator cuff syndrome	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma metastatic	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Nervous system disorders
Basal ganglia inferction	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Cerebrovascular accident	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Convulsion	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Presyncope	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Syncope	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Transient ischaemic attack	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Vocal cord paralysis	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Encephalopathy	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
Hypoglcaemic seizure	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
Psychiatric disorders
Mental status changes	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Renal and urinary disorders
Renal failure acute	1/103 (1%)	1	1/153 (0.7%)	1	0/42 (0%)	0
Renal failure chronic	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
Obstructive uropathy	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	2/103 (1.9%)	2	0/153 (0%)	0	0/42 (0%)	0
Chronic obstructive pulmonary disease	1/103 (1%)	1	1/153 (0.7%)	1	0/42 (0%)	0
Acute respiratory failure	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Pulmonary embolism	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulcer	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Vascular disorders
Deep vein thrombosis	1/103 (1%)	1	0/153 (0%)	0	0/42 (0%)	0
Hypertension	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Hypertensive emergency	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Orthostatic hypotension	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Peripheral vascular disorder	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Thrombophlebitis	0/103 (0%)	0	1/153 (0.7%)	1	0/42 (0%)	0
Hypertensive crisis	0/103 (0%)	0	0/153 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	CTAP101 Capsules (Not Randomized; 6 Mos Treatment)		CTAP101 Capsules (Not Randomized; 12 Mos Treatment)		CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/103 (35%)		54/153 (35.3%)		22/42 (52.4%)
Blood and lymphatic system disorders
Anaemia	7/103 (6.8%)	7	9/153 (5.9%)	9	2/42 (4.8%)	2
Gastrointestinal disorders
Constipation	7/103 (6.8%)	7	6/153 (3.9%)	6	0/42 (0%)	0
Diarrhoea	7/103 (6.8%)	7	6/153 (3.9%)	6	1/42 (2.4%)	1
Nausea	8/103 (7.8%)	8	5/153 (3.3%)	5	2/42 (4.8%)	2
General disorders
Oedema peripheral	6/103 (5.8%)	6	5/153 (3.3%)	5	0/42 (0%)	0
Fatigue	7/103 (6.8%)	7	3/153 (2%)	3	1/42 (2.4%)	1
Oedema	2/103 (1.9%)	2	2/153 (1.3%)	2	3/42 (7.1%)	3
Infections and infestations
Urinary tract obstruction	2/103 (1.9%)	2	10/153 (6.5%)	10	1/42 (2.4%)	1
Investigations
Blood creatinine increased	3/103 (2.9%)	3	6/153 (3.9%)	6	3/42 (7.1%)	3
Metabolism and nutrition disorders
Gout	7/103 (6.8%)	7	2/153 (1.3%)	2	1/42 (2.4%)	1
Hyperphosphatemia	2/103 (1.9%)	2	3/153 (2%)	3	4/42 (9.5%)	4
Hypoglycaemia	1/103 (1%)	1	3/153 (2%)	3	3/42 (7.1%)	3
Hyperkalaemia	1/103 (1%)	1	0/153 (0%)	0	3/42 (7.1%)	3
Respiratory, thoracic and mediastinal disorders
Cough	5/103 (4.9%)	5	4/153 (2.6%)	4	3/42 (7.1%)	3
Vascular disorders
Hypertension	4/103 (3.9%)	4	6/153 (3.9%)	6	3/42 (7.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.