A Double-blind, Double-dummy, Parallel, Active-controlled, Randomized Trial to Evaluate Efficacy & Safety in Anemia Subjects

• ClinicalTrials.gov Identifier: NCT01425463
• Recruitment Status: Completed
• First Posted: August 30, 2011
• Results First Posted: November 6, 2014
• Last Update Posted: June 1, 2015
• Sponsor: Sanol GmbH
• Information provided by (Responsible Party): UCB Pharma ( Sanol GmbH )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Iron Deficiency Anemia
• Interventions: Drug: Ferrous (II) Glycine Sulphate Complex; Drug: Polyferose; Other: Placebo to Ferrous (II) Glycine Sulphate Complex; Other: Placebo to Polyferose
• Enrollment: 256

Participant Flow

Recruitment Details	This multicenter study started to enroll subjects in March 2011 in order to end up with 16 centers in China with enrolled subjects.
Pre-assignment Details	Participant Flow refers to the Randomized Set (RS). The RS includes all subjects who have a randomization number recorded on the Case Report Form (CRF).

Arm/Group Title	Ferrous (II) Glycine Sulphate Complex	Polyferose
Arm/Group Description	Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.	Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.
Period Title: Overall Study
Started	130	126
Safety Set	126	122
Full Analysis Set	122	116
Completed	106	102
Not Completed	24	24
Reason Not Completed
Adverse Event	5	7
Lack of Efficacy	1	1
Protocol Violation	2	2
Lost to Follow-up	5	2
Withdrawal by Subject	7	5
Unknown Reason	4	7

Baseline Characteristics

Arm/Group Title		Ferrous (II) Glycine Sulphate Complex	Polyferose	Total
Arm/Group Description		Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.	Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.	Total of all reporting groups
Overall Number of Baseline Participants		122	116	238
Baseline Analysis Population Description		Baseline Characteristics refer to the Full Analysis Set (FAS). FAS consists of all enrolled subjects who took at least one dose of study medicine and have at least one post-baseline effectiveness measurement (Hemoglobin-value). It also includes subjects with protocol deviance and incomplete data due to withdrawal.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	122 participants	116 participants	238 participants
		37.2 (8.5)	37.8 (7.9)	37.5 (8.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	122 participants	116 participants	238 participants
	Female	122 100.0%	115 99.1%	237 99.6%
	Male	0 0.0%	1 0.9%	1 0.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	122 participants	116 participants	238 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	122 100.0%	116 100.0%	238 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
China	Number Analyzed	122 participants	116 participants	238 participants
		122	116	238
Weight; Mean (Standard Deviation); Unit of measure: Kilogram (kg)
	Number Analyzed	122 participants	116 participants	238 participants
		58.2 (7.8)	58.1 (7.6)	58.1 (7.7)
Height; Mean (Standard Deviation); Unit of measure: Centimeter (cm)
	Number Analyzed	122 participants	116 participants	238 participants
		161.2 (4.4)	161.2 (4.6)	161.2 (4.5)

Outcome Measures

1. Primary Outcome

Title	Change in Hemoglobin (Hb) From Baseline (Week 0) to Week 12
Description	[Not Specified]
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Per-Protocol Set (PPS), which is defined as a subset of the FAS, excluding all subjects with protocol deviations considered important for the subjects' validity concerning the efficacy analysis.

Arm/Group Title	Ferrous (II) Glycine Sulphate Complex	Polyferose
Arm/Group Description:	Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.	Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.
Overall Number of Participants Analyzed	95	92
Mean (Standard Deviation); Unit of Measure: gramm per liter (g/L)
	31.47 (23.77)	31.92 (21.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ferrous (II) Glycine Sulphate Complex, Polyferose
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Noninferiority of the investigational drug (Ferrous (II) Glycine Sulphate Complex) to the reference drug (Polyferose) was concluded if the lower limit of the two-sided 95 % confidence interval was greater than -7.0 g/L.
Method of Estimation	Estimation Parameter	LS-Mean of ANCOVA
	Estimated Value	-2.19
	Confidence Interval	(2-Sided) 95%; -8.47 to 4.09
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change in Hemoglobin (Hb) From Baseline (Week 0) to Week 2
Description	[Not Specified]
Time Frame	From Baseline to Week 2

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Per-Protocol Set (PPS), which is defined as a subset of the FAS, excluding all subjects with protocol deviations considered important for the subjects' validity concerning the efficacy analysis.

Arm/Group Title	Ferrous (II) Glycine Sulphate Complex	Polyferose
Arm/Group Description:	Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.	Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.
Overall Number of Participants Analyzed	93	91
Mean (Standard Deviation); Unit of Measure: gramm per liter (g/L)
	12.29 (13.60)	12.79 (13.13)

3. Secondary Outcome

Title	Change in Hemoglobin (Hb) From Baseline (Week 0) to Week 4
Description	[Not Specified]
Time Frame	From Baseline to Week 4

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Per-Protocol Set (PPS), which is defined as a subset of the FAS, excluding all subjects with protocol deviations considered important for the subjects' validity concerning the efficacy analysis.

Arm/Group Title	Ferrous (II) Glycine Sulphate Complex	Polyferose
Arm/Group Description:	Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.	Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.
Overall Number of Participants Analyzed	95	92
Mean (Standard Deviation); Unit of Measure: gramm per liter (g/L)
	20.37 (19.63)	20.16 (17.46)

4. Secondary Outcome

Title	Change in Hemoglobin (Hb) From Baseline (Week 0) to Week 8
Description	[Not Specified]
Time Frame	From Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Per-Protocol Set (PPS), which is defined as a subset of the FAS, excluding all subjects with protocol deviations considered important for the subjects' validity concerning the efficacy analysis.

Arm/Group Title	Ferrous (II) Glycine Sulphate Complex	Polyferose
Arm/Group Description:	Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.	Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.
Overall Number of Participants Analyzed	95	92
Mean (Standard Deviation); Unit of Measure: gramm per liter (g/L)
	26.57 (22.67)	28.33 (20.90)

5. Secondary Outcome

Title	Percentage of Responders at Week 12
Description	Responders are defined as having an increment of Hemoglobin (Hb) > 15 g/L and post-treatment Hb > 120 g/L (male) or > 110 g/L (female) at Visit 6 (Week 12).
Time Frame	End of Treatment Period (Week 12)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Per-Protocol Set (PPS), which is defined as a subset of the FAS, excluding all subjects with protocol deviations considered important for the subjects' validity concerning the efficacy analysis.

Arm/Group Title	Ferrous (II) Glycine Sulphate Complex	Polyferose
Arm/Group Description:	Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.	Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.
Overall Number of Participants Analyzed	95	92
Measure Type: Number; Unit of Measure: percentage of participants
	71.6	80.4

Adverse Events

Time Frame	Adverse Events were collected up to 14 weeks from Baseline to the Safety Follow-Up Visit.
Adverse Event Reporting Description	Adverse Events refer to the Safety Set (SS). SS represents all subjects included in the study who took at least one dose of study medication and have at least one safety evaluation after that.
Arm/Group Title	Ferrous (II) Glycine Sulphate Complex		Polyferose
Arm/Group Description	Ferrous (II) Glycine Sulphate Complex treatment with 567.7 mg three times a day (t.i.d.) for 12 weeks plus Placebo to Polyferose. Ferrous (II) Glycine Sulphate Complex: Oral dose of 567.7 mg Ferrous (II) Glycine Sulphate Complex three times a day (t.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Polyferose: Administered orally with water.		Polyferose treatment with 150 mg twice daily (b.i.d) for 12 weeks plus Placebo to Ferrous (II) Glycine Sulphate Complex. Polyferose: Oral dose of 150 mg Polyferose Capsules twice daily (b.i.d) for 12 weeks (equivalent to 300 mg iron element per day for 12 weeks). Administered orally with water. Placebo to Ferrous (II) Glycine Sulphate Complex: Administered orally with water.
All-Cause Mortality
	Ferrous (II) Glycine Sulphate Complex		Polyferose
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Ferrous (II) Glycine Sulphate Complex		Polyferose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/126 (2.38%)		3/122 (2.46%)
Infections and infestations
Measles * 1	1/126 (0.79%)	1	0/122 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma * 1	0/126 (0.00%)	0	1/122 (0.82%)	1
Nervous system disorders
Subarachnoid haemorrhage * 1	0/126 (0.00%)	0	1/122 (0.82%)	1
Surgical and medical procedures
Abortion induced * 1	2/126 (1.59%)	2	1/122 (0.82%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ferrous (II) Glycine Sulphate Complex		Polyferose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/126 (17.46%)		25/122 (20.49%)
Gastrointestinal disorders
Diarrhoea * 1	9/126 (7.14%)	10	11/122 (9.02%)	14
Abdominal pain * 1	7/126 (5.56%)	9	5/122 (4.10%)	6
Melaena * 1	6/126 (4.76%)	6	8/122 (6.56%)	9
Nausea * 1	3/126 (2.38%)	3	7/122 (5.74%)	7
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB Clinical Trial Call Center
• Organization: UCB
• Phone: +1 877 822 9493 (UCB)

• Responsible Party: UCB Pharma ( Sanol GmbH )
• ClinicalTrials.gov Identifier: NCT01425463
• Other Study ID Numbers: SP0986; 2014-004380-20 ( EudraCT Number )
• First Submitted: August 26, 2011
• First Posted: August 30, 2011
• Results First Submitted: October 30, 2014
• Results First Posted: November 6, 2014
• Last Update Posted: June 1, 2015