Alprostadil in Maculopathy Study (AIMS)

• ClinicalTrials.gov Identifier: NCT00619229
• Recruitment Status: Terminated
• First Posted: February 20, 2008
• Results First Posted: April 11, 2011
• Last Update Posted: October 27, 2014
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Macular Degeneration
• Interventions: Drug: Alprostadil (prostaglandin E1); Other: Placebo
• Enrollment: 37

Participant Flow

Recruitment Details	The Full Analysis Set (FAS) includes all randomized subjects treated with at least one infusion and having valid Baseline and Post-Baseline measurements. The Randomized Set (RS) consists of all randomized subjects who have completed Visit 16 or terminated prematurely.
Pre-assignment Details	Participant Flow shows the RS. Baseline Characteristics refer to the FAS.

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Period Title: Overall Study
Started	18	18
Full Analysis Set (FAS)	16	17
Completed	14	16
Not Completed	4	2
Reason Not Completed
Withdrawal by Subject	1	1
Lost to Follow-up	1	0
Termination of the Study by the Sponsor	1	1
Investigator planned Cataract Operation	1	0

Baseline Characteristics

Arm/Group Title		Alprostadil	Placebo	Total
Arm/Group Description		Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days	Total of all reporting groups
Overall Number of Baseline Participants		16	17	33
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants	17 participants	33 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	1 6.3%	4 23.5%	5 15.2%
	>=65 years	15 93.8%	13 76.5%	28 84.8%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	16 participants	17 participants	33 participants
		76.1 (8.5)	71.7 (8.1)	73.8 (8.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants	17 participants	33 participants
	Female	6 37.5%	9 52.9%	15 45.5%
	Male	10 62.5%	8 47.1%	18 54.5%
White; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	16 participants	17 participants	33 participants
		16	17	33
Weight; Mean (Standard Deviation); Unit of measure: Kilogramm (kg)
	Number Analyzed	16 participants	17 participants	33 participants
		77.14 (14.71)	76.46 (14.49)	76.79 (14.37)
Height (cm); Mean (Standard Deviation); Unit of measure: Centimeter (cm)
	Number Analyzed	16 participants	17 participants	33 participants
		171.06 (9.29)	168.59 (8.69)	169.79 (8.93)
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kg/ (m^2)
	Number Analyzed	16 participants	17 participants	33 participants
		26.20 (3.38)	26.70 (3.32)	26.45 (3.31)

Outcome Measures

1. Primary Outcome

Title	Difference in Visual Acuity Between Measurements at 3 Months After Drug Intervention and Measurements at Baseline (Assessed Within Early Treatment Diabetic Retinopathy Study (ETDRS) Chart)
Description	Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly.
Time Frame	From baseline to 3 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Mean (Standard Deviation); Unit of Measure: Lines read in ETDRS chart
	0.94 (1.84)	0.53 (1.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alprostadil, Placebo
	Comments	The primary goal of the study was to test the following null hypothesis: H0: μAlprostadil ≤ μPlacebo, against the alternative hypothesis H1: μAlprostadil > μPlacebo, where μ denotes the mean differences in visual acuity between measurements at 3 months after the end of study drug infusion minus measurements at baseline as assessed as line difference on the standard ETDRS charts.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1220
	Comments	The criterion for significance (α) was set at one-sided α = 0.025, which means that only an effect in the expected direction was interpreted.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; -0.674 to 2.55
	Estimation Comments	For exploratory testing an Analysis of Variance-Covariance (ANCOVA) F-test with dependent variable 'difference in visual acuity', fixed factors 'treatment' and 'centre' and Baseline value as a covariate was used.

2. Secondary Outcome

Title	The Difference in Visual Acuity Between Measurements Immediately After Intervention and Measurements at Baseline
Description	Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly.
Time Frame	From baseline to time immediately after intervention

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Mean (Standard Deviation); Unit of Measure: Lines read in ETDRS chart
	1.29 (1.44)	0.38 (1.54)

3. Secondary Outcome

Title	The Difference in Visual Acuity Between Measurements at 6 Months After Intervention and Measurements at Baseline
Description	Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly.
Time Frame	From baseline to 6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Mean (Standard Deviation); Unit of Measure: Lines read in ETDRS chart
	1.31 (1.45)	0.29 (2.11)

4. Secondary Outcome

Title	Progression of the Dry Age-related Macular Degeneration
Description	Severity of the diagnosed dry age-related macular degeneration (AMD) was assessed in comparison to Baseline and classified as; Progression; Stabilization; Amelioration
Time Frame	From baseline to 6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Measure Type: Number; Unit of Measure: Participants
Progression in disease	11	10
Stabilization of disease	1	3
Amelioration of disease	4	4

5. Secondary Outcome

Title	Development of a Wet Age-related Macular Degeneration
Description	A wet age-related macular degeneration (AMD) is defined as the development of choroidal neovascularization of the "study-eye" (worse eye). Development is categorized in Yes and No, where Yes means that a subject who had no wet AMD at Screening has developed a wet AMD at Week 29.
Time Frame	From baseline to 6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Measure Type: Number; Unit of Measure: Participants
Yes	0	0
No	16	17

6. Secondary Outcome

Title	The Difference in Contrast Sensitivity Between Measurements Immediately After Intervention and Measurements at Baseline
Description	Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability.
Time Frame	From baseline to time immediately after intervention

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Mean (Standard Deviation); Unit of Measure: Unit on a scale
	0.009 (0.282)	0.018 (0.224)

7. Secondary Outcome

Title	The Difference in Contrast Sensitivity Between Measurements at 3 Months After Intervention and Measurements at Baseline
Description	Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability.
Time Frame	From baseline to 3 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Mean (Standard Deviation); Unit of Measure: Unit on a scale
	0.084 (0.205)	-0.026 (0.324)

8. Secondary Outcome

Title	The Difference in Contrast Sensitivity Between Measurements at 6 Months After Intervention and Measurements at Baseline
Description	Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability.
Time Frame	From baseline to 6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Mean (Standard Deviation); Unit of Measure: Unit on a scale
	0.028 (0.221)	0.009 (0.373)

9. Secondary Outcome

Title	The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline
Description	The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'.
Time Frame	From baseline to time immediately after intervention

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Measure Type: Number; Unit of Measure: Participants
Changed from Normal to Pathologic	1	0
Finding unchanged	15	13
Changed from Pathologic to Normal	0	4

10. Secondary Outcome

Title	The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline
Description	The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'.
Time Frame	From baseline to 3 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Measure Type: Number; Unit of Measure: Participants
Changed from Normal to Pathologic	1	0
Finding unchanged	13	14
Changed from Pathologic to Normal	2	3

11. Secondary Outcome

Title	The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline
Description	The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'.
Time Frame	From baseline to 6 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Alprostadil	Placebo
Arm/Group Description:	Alprostadil 60 mcg/day i.v. for 15 days	Placebo i.v. for 15 days
Overall Number of Participants Analyzed	16	17
Measure Type: Number; Unit of Measure: Participants
Changed from Normal to Pathologic	1	0
Finding unchanged	12	15
Changed from Pathologic to Normal	3	2

Adverse Events

Time Frame	Adverse Events (AEs) were collected up to 33 weeks from first dose of trial medication on Day 1 to the last Follow-up Visit.
Adverse Event Reporting Description	AEs refer to the Safety Set (SS). The SS includes all randomized subjects who completed Visit 16 or terminated prematurely and who received at least one dose of trial medication.
Arm/Group Title	Alprostadil		Placebo
Arm/Group Description	Alprostadil 60 mcg/day i.v. for 15 days		Placebo i.v. for 15 days
All-Cause Mortality
	Alprostadil		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Alprostadil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0.00%)		0/18 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Alprostadil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/18 (11.11%)		6/18 (33.33%)
Eye disorders
Choroidal Neovascularisation * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
Visual Disturbance * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
Vitreous Opacities * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
Gastrointestinal disorders
Nausea * 1	1/18 (5.56%)	1	0/18 (0.00%)	0
Abdominal Pain Upper * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
General disorders
Fatigue * 1	1/18 (5.56%)	1	0/18 (0.00%)	0
Infections and infestations
Nasopharyngitis * 1	1/18 (5.56%)	1	1/18 (5.56%)	1
Investigations
Blood Pressure decreased * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
Nervous system disorders
Dizziness * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
Headache * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
Paraesthesia * 1	0/18 (0.00%)	0	1/18 (5.56%)	1
Vascular disorders
Phlebitis * 1	1/18 (5.56%)	1	0/18 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (11.0)

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.

UCB has > 60 days but <= 180 days to review results communications prior to public release and may delete information that is confidential and compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Results Point of Contact

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

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00619229
• Other Study ID Numbers: SP0878; 2005-005686-11 ( EudraCT Number )
• First Submitted: December 24, 2007
• First Posted: February 20, 2008
• Results First Submitted: January 27, 2011
• Results First Posted: April 11, 2011
• Last Update Posted: October 27, 2014