Placebo Controlled Efficacy and Safety Study of CD2475/101 40 mg Tablets vs. Placebo and Doxycycline 100 mg Capsules Once Daily in the Treatment of Inflammatory Lesions of Acne Vulgaris

• Sponsor: Galderma R&D (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01320033
• Collaborator: (none)
• Enrollment: 662
• Locations: 31
• Arms: 3
• Actual Duration (Months): 9.2
• Patients Per Site: 21.4
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The primary objectives of the study is to show CD2475/101 40mg tablets taken once a day for 16 weeks is superior to the placebo in Change from baseline to Week 16(Last Observation Carry Forward, Intent To Treat) in inflammatory lesion counts.

Condition or Disease	Intervention/Treatment	Phase
Acne Vulgaris	Drug: CD2475/101 40 mg; Drug: Doxycycline 100 mg; Drug: Placebo	Phase 2

Detailed Description

Investigator's global assessment and lesion count will be performed at each study visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 662 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi Center, Randomized, Double Blind, Placebo Controlled, 3 Arm, Parallel Group Study Comparing the Efficacy and Safety of CD2475/101 40 mg Tablets Versus Placebo and Doxycycline 100 mg Capsules Once Daily in the Treatment of Inflammatory Lesions in Subjects With Acne Vulgaris
• Actual Study Start Date: Mar 29, 2011
• Actual Primary Completion Date: Jan 3, 2012
• Actual Study Completion Date: Jan 3, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CD2475/101 40 mg Participants receive 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Drug: CD2475/101 40 mg; Participants receive 40 mg of CD2475/101 tablets once a day for 16 weeks.; Drug: Placebo; Participants receive matching placebo tablet, matching placebo capsule once a day for 16 weeks.
Active Comparator: Doxycycline 100 mg Participants receive 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Drug: Doxycycline 100 mg; Participants receive 100 mg of Doxycycline capsule once a day for 16 weeks; Drug: Placebo; Participants receive matching placebo tablet, matching placebo capsule once a day for 16 weeks.
Placebo Comparator: Placebo Participants receive matching placebo tablet plus placebo capsule orally once daily for 16 weeks.	Drug: Placebo; Participants receive matching placebo tablet, matching placebo capsule once a day for 16 weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) [From Baseline up to Week 16 (LOCF)]

   The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported.

Secondary Outcome Measures

1. Investigator Global Assessment (IGA) Success Rate at Week 16 (Last Observation Carried Forward [LOCF]) [Week 16 (LOCF)]

   IGA scale consisted of 5 grades (0-4) among which 0= Clear (no evidence of papules or pustules [inflammatory lesions]), 1= Almost clear (rare non-inflamed papules (papules must be resolving and hyperpigmented, though not pink-red), 2= Mild (few inflammatory lesions [papules/pustules only; no nodulo-cystic lesions]), 3=Moderate (multiple inflammatory lesions evident: many papules/pustules; up to two nodulocystic lesions), 4= Severe (inflammatory lesions are more apparent, many papules/pustules, few nodulo-cystic lesions). Success rate was defined as percentage of participants who achieved an Investigator Global Assessment (IGA) score of 1 (almost clear) or 0 (Clear) and at least a 2-grade improvement from Baseline to Week 16 (LOCF).

2. Percent Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) [From Baseline up to Week 16 (LOCF)]

   The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Percent change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported.

3. Percent Change From Baseline in Total Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) [From Baseline up to Week 16 (LOCF)]

   Total lesions were the sum of inflammatory lesion counts, non-inflammatory lesion counts, nodules and cysts. Percentage change from baseline in total lesion counts to Week 16 were reported.

4. Change From Baseline in Non-Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) [From Baseline up to Week 16 (LOCF)]

   The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). Change from baseline in non-inflammatory lesion counts to week 16 were reported

5. Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 [Baseline, Week 12, and Week 16]

   Global assessments for inflammatory lesions of truncal acne were done separately on back and chest. The global assessments severity scale included 5 grades (0-4): where in 0= Clear-no evidence of papules or pustules (inflammatory lesions), 1= Almost clear- rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red), 2=Mild- few inflammatory lesions (papules/pustules only; no nodulo-cystic lesions), 3=Moderate- multiple inflammatory lesions evident: many papules/pustules; may be a few nodulocystic lesions, 4=Severe- inflammatory lesions are more apparent, many papules/pustules, may be a few nodulo-cystic lesions.

6. Number of Participants With at Least One Adverse Event (AE) [From Baseline up to Week 16]

   An AE was any untoward medical occurrence in a participant or clinical investigation participants administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Number of participants with at least one AE were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female subjects 12 years of age or older

• acne vulgaris with facial involvement

• A score of 3 (Moderate) or 4 (Severe) on the Investigator's Global Assessment Scale (inflammatory)

• 25 to 75 inflammatory lesions (papules and pustules) on the face (including the nose)

Exclusion Criteria:

• More than two acne nodules/cysts on the face

• Acne conglobata, acne fulminans, secondary acne (chloracne, drug induced acne, etc.), or severe acne requiring systemic retinoid treatment

• Underlying diseases or other dermatologic conditions that require the use of interfering topical or systemic therapy such as, but not limited to, atopic dermatitis, perioral dermatitis or rosacea

• Beard or facial hair which might interfere with study assessments

• planning excessive exposure to sun or ultraviolet light during the study (i.e. natural or artificial sunlight, including tanning booths and sun lamp)

• Use of oral contraceptives solely for control of acne

• Liver function test alanine transaminase (ALT) and/or aspartate transaminase (AST) 2.5 times above upper limit of normal

• Renal function test serum creatinine at 150 umol/L (17 mg/L) or higher

• Presence of oral or genital candidiasis or history of multiple episodes of oral or genital candidiasis

• Females who intend to conceive a child within 5 months following Baseline visit

• Males who intend to conceive a child with partner during the study period

• Requiring concomitant use of methoxyflurane

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Burke Pharmaceutical Research	Hot Springs	Arkansas	United States	71913
2	Dermatology Research Associates, Inc.	Los Angeles	California	United States	90045
3	Colorado Medical Research Center	Denver	Colorado	United States	80210
4	Longmont Medical Research Network	Longmont	Colorado	United States	80501
5	International Dermatology Research, Inc.	Miami	Florida	United States	33144
6	MedaPhase, Inc.	Newnan	Georgia	United States	30263
7	Dermatology Specialists PC	Louisville	Kentucky	United States	40202
8	Somerset Skin Care Center	Troy	Michigan	United States	48084
9	Grekin Skin Care	Warren	Michigan	United States	48088
10	Central Dermatology, PC	Saint Louis	Missouri	United States	63117
11	Skin Specialists, PC	Omaha	Nebraska	United States	68144
12	Academic Dermatology	Albuquerque	New Mexico	United States	87106
13	Helendale Dermatology & Medical Spa	Rochester	New York	United States	14609
14	Dermatology Consulting Services	High Point	North Carolina	United States	27262
15	PMG Research of Wilmington	Wilmington	North Carolina	United States	28401
16	Haber Dermatology & cosmetic Surgery, Inc	South Euclid	Ohio	United States	44118
17	Central Sooner Research	Norman	Oklahoma	United States	73069
18	Oregon Dermatology & Research Center	Portland	Oregon	United States	97210
19	Stephen Schleicher	Hazleton	Pennsylvania	United States	18201
20	Palmetto Clinical Trial Services, LLC	Greenville	South Carolina	United States	29607
21	Dermatology Research Associates	Nashville	Tennessee	United States	37203
22	Tennessee Clinical Research Center	Nashville	Tennessee	United States	37215
23	Arlington Center for Dermatology	Arlington	Texas	United States	76011
24	Derm Research, Inc	Austin	Texas	United States	78759
25	J&S Studies	College Station	Texas	United States	77845
26	Suzanne Bruce and associates P.A. The Center for skin Research	Houston	Texas	United States	77056
27	Center for Clinical Studies	Houston	Texas	United States	77058
28	Progressive Clinical Research	San Antonio	Texas	United States	78229
29	Stephen Miller MD	San Antonio	Texas	United States	78229
30	Dermatology Research Center	Salt Lake City	Utah	United States	84124
31	Premier Clinical Research	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Galderma R&D

Investigators

• Study Director: Michael Graeber, MD, Galderma R&D

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Galderma R&D
• ClinicalTrials.gov Identifier: NCT01320033
• Other Study ID Numbers: RD.06.SPR.18195
• First Posted: Mar 22, 2011
• Last Update Posted: Feb 18, 2021
• Last Verified: Dec 1, 2019

• Keywords provided by Galderma R&D: acne vulgaris; inflammatory lesions
• Additional relevant MeSH terms: Acne Vulgaris; Doxycycline

Study Results

Participant Flow

Recruitment Details	This study was conducted in United States between 29 March 2011 (first participant first visit) to 3 January 2012 (last participant last visit).
Pre-assignment Detail	A total of 662 participants randomized the study and dispensed with study drug out of which 487 completed study.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 milligrams (mg) of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Period Title: Overall Study
STARTED	216	224	222
COMPLETED	158	160	169
NOT COMPLETED	58	64	53

Baseline Characteristics

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo	Total
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.	Total of all reporting groups
Overall Participants	216	224	222	662
Age (Count of Participants)
<=18 years	123 56.9%	132 58.9%	133 59.9%	388 58.6%
Between 18 and 65 years	93 43.1%	92 41.1%	89 40.1%	274 41.4%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	19.6 (7.70)	19.6 (7.54)	18.7 (6.34)	19.3 (7.21)
Sex: Female, Male (Count of Participants)
Female	115 53.2%	121 54%	115 51.8%	351 53%
Male	101 46.8%	103 46%	107 48.2%	311 47%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	35 16.2%	30 13.4%	37 16.7%	102 15.4%
Not Hispanic or Latino	181 83.8%	194 86.6%	185 83.3%	560 84.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	4 1.9%	7 3.1%	7 3.2%	18 2.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	47 21.8%	49 21.9%	40 18%	136 20.5%
White	159 73.6%	163 72.8%	170 76.6%	492 74.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	6 2.8%	5 2.2%	5 2.3%	16 2.4%
Region of Enrollment (participants) [Number]
United States	216 100%	224 100%	222 100%	662 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
Description	The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported.
Time Frame	From Baseline up to Week 16 (LOCF)

Outcome Measure Data

Analysis Population Description

Intent To Treat (ITT) population consisted of all participants who were randomized and to whom study drug was dispensed.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Measure Participants	216	224	222
Mean (Standard Deviation) [lesion count]	-16.1 (11.39)	-12.9 (14.60)	-12.6 (16.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CD2475/101 40 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.6
	Confidence Interval	(2-Sided) 95%; -6.1 to -1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CD2475/101 40 mg, Doxycycline 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -5.4 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Doxycycline 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.595
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.2 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Investigator Global Assessment (IGA) Success Rate at Week 16 (Last Observation Carried Forward [LOCF])
Description	IGA scale consisted of 5 grades (0-4) among which 0= Clear (no evidence of papules or pustules [inflammatory lesions]), 1= Almost clear (rare non-inflamed papules (papules must be resolving and hyperpigmented, though not pink-red), 2= Mild (few inflammatory lesions [papules/pustules only; no nodulo-cystic lesions]), 3=Moderate (multiple inflammatory lesions evident: many papules/pustules; up to two nodulocystic lesions), 4= Severe (inflammatory lesions are more apparent, many papules/pustules, few nodulo-cystic lesions). Success rate was defined as percentage of participants who achieved an Investigator Global Assessment (IGA) score of 1 (almost clear) or 0 (Clear) and at least a 2-grade improvement from Baseline to Week 16 (LOCF).
Time Frame	Week 16 (LOCF)

Outcome Measure Data

Analysis Population Description

ITT Population consisted of all participants who were randomized and to whom study drug was dispensed.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Measure Participants	216	224	222
Number [Percentage of participants]	14.4 6.7%	13.8 6.2%	7.7 3.5%

3. Secondary Outcome

Title	Percent Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
Description	The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Percent change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported.
Time Frame	From Baseline up to Week 16 (LOCF)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were randomized and to whom study drug was dispensed.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Measure Participants	216	224	222
Mean (Standard Deviation) [percent change]	-48.6 (31.72)	-40.3 (40.90)	-37.1 (44.45)

4. Secondary Outcome

Title	Percent Change From Baseline in Total Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
Description	Total lesions were the sum of inflammatory lesion counts, non-inflammatory lesion counts, nodules and cysts. Percentage change from baseline in total lesion counts to Week 16 were reported.
Time Frame	From Baseline up to Week 16 (LOCF)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were randomized and to whom study drug was dispensed.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Measure Participants	216	224	222
Mean (Standard Deviation) [percent change]	-38.3 (32.24)	-27.8 (43.94)	-27.8 (38.05)

5. Secondary Outcome

Title	Change From Baseline in Non-Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
Description	The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). Change from baseline in non-inflammatory lesion counts to week 16 were reported
Time Frame	From Baseline up to Week 16 (LOCF)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were randomized and to whom study drug was dispensed.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Measure Participants	216	224	222
Mean (Standard Deviation) [lesion count]	-10.0 (21.49)	-5.2 (21.60)	-5.8 (18.19)

6. Secondary Outcome

Title	Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16
Description	Global assessments for inflammatory lesions of truncal acne were done separately on back and chest. The global assessments severity scale included 5 grades (0-4): where in 0= Clear-no evidence of papules or pustules (inflammatory lesions), 1= Almost clear- rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red), 2=Mild- few inflammatory lesions (papules/pustules only; no nodulo-cystic lesions), 3=Moderate- multiple inflammatory lesions evident: many papules/pustules; may be a few nodulocystic lesions, 4=Severe- inflammatory lesions are more apparent, many papules/pustules, may be a few nodulo-cystic lesions.
Time Frame	Baseline, Week 12, and Week 16

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were randomized and to whom study drug was dispensed.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Measure Participants	216	224	222
Baseline : Lesion of Truncal Acne on Back	1.6 (1.10)	1.5 (1.09)	1.5 (1.07)
Baseline : Lesion of Truncal Acne on Chest	1.2 (1.04)	1.2 (1.00)	1.1 (0.98)
Week 12 : Lesions of Truncal Acne on Back	1.2 (1.06)	1.1 (1.05)	1.2 (1.04)
Week 12 : Lesion of Truncal Acne on Chest	0.9 (0.94)	0.9 (0.99)	0.9 (0.95)
Week 16 : Lesions of Truncal Acne on Back	1.1 (1.06)	1.0 (1.06)	1.2 (1.03)
Week 16 : Lesion of Truncal Acne on Chest	0.9 (1.01)	0.8 (0.93)	0.9 (0.95)

7. Secondary Outcome

Title	Number of Participants With at Least One Adverse Event (AE)
Description	An AE was any untoward medical occurrence in a participant or clinical investigation participants administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Number of participants with at least one AE were reported.
Time Frame	From Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all participants who received at least one dose of study drug.

Arm/Group Title	CD2475/101 40 mg	Doxycycline 100 mg	Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.	Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.	Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks.
Measure Participants	216	223	222
Count of Participants [Participants]	63 29.2%	83 37.1%	89 40.1%

Adverse Events

Time Frame	From Baseline up to Week 16
Arm/Group Title	CD2475/101 40 mg		Doxycycline 100 mg		Placebo
Arm/Group Description	Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks.		Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.		Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks.
All Cause Mortality
	CD2475/101 40 mg		Doxycycline 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/216 (0%)		0/223 (0%)		0/222 (0%)
Serious Adverse Events
	CD2475/101 40 mg		Doxycycline 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/216 (0.5%)		4/223 (1.8%)		2/222 (0.9%)
Blood and lymphatic system disorders
Coagulopathy	0/216 (0%)		0/223 (0%)		1/222 (0.5%)
Injury, poisoning and procedural complications
Forearm fracture	0/216 (0%)		1/223 (0.4%)		0/222 (0%)
Fall	0/216 (0%)		1/223 (0.4%)		0/222 (0%)
Multiple drug overdose intentional	0/216 (0%)		0/223 (0%)		1/222 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/216 (0%)		1/223 (0.4%)		0/222 (0%)
Nervous system disorders
Multiple sclerosis relapse	0/216 (0%)		0/223 (0%)		1/222 (0.5%)
Hepatic encephalopathy	0/216 (0%)		0/223 (0%)		1/222 (0.5%)
Psychiatric disorders
Affective disorder	1/216 (0.5%)		0/223 (0%)		0/222 (0%)
Suicide attempt	0/216 (0%)		0/223 (0%)		1/222 (0.5%)
Depression	0/216 (0%)		1/223 (0.4%)		1/222 (0.5%)
Skin and subcutaneous tissue disorders
Urticaria	0/216 (0%)		1/223 (0.4%)		0/222 (0%)
Other (Not Including Serious) Adverse Events
	CD2475/101 40 mg		Doxycycline 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/216 (13.4%)		51/223 (22.9%)		29/222 (13.1%)
Gastrointestinal disorders
Nausea	7/216 (3.2%)		14/223 (6.3%)		4/222 (1.8%)
Vomiting	1/216 (0.5%)		15/223 (6.7%)		5/222 (2.3%)
Infections and infestations
Nasopharyngitis	7/216 (3.2%)		7/223 (3.1%)		14/222 (6.3%)
Nervous system disorders
Headache	14/216 (6.5%)		15/223 (6.7%)		6/222 (2.7%)

Limitations/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.