A Study of RO7123520 to Evaluate the Safety and Efficacy... | NCT03001219

NCT03001219

ID	Type	Description	Link
2016-002126-36	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: Placebo	Placebo Comparator	Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha Drug: Methotrexate Drug: Placebo
Part 1: RO7123520	Experimental	Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha Drug: Methotrexate Drug: RO7123520
Part 2: Placebo	Placebo Comparator	Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha Drug: Methotrexate Drug: Placebo
Part 2: RO7123520	Experimental	Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.	Drug: Anti-TNF-alpha Drug: Methotrexate Drug: RO7123520
Part 3: Placebo	Placebo Comparator	Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate. NOTE: Part 3 was not conducted.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Anti-TNF-alpha	Drug	Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.	Part 1: Placebo Part 1: RO7123520 Part 2: Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Baseline to last participant last visit (approximately 2 years)
Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12	The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.	Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
Percentage of Participants With Anti-Drug Antibodies		Baseline
Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans		Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12	The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of adult-onset RA as defined by the ACR 2010 criteria, for at least 6 months before screening
Moderately to severely active RA as defined by at least 4/28 tender joints and at least 4/28 swollen joints, and a DAS28 greater than or equal to (≥) 3.2
For Part 2 only: Active synovitis and/or osteitis as determined by contrast-enhanced magnetic resonance imaging
Participants must be taking stable dose of anti-TNF-alpha therapies
Participants on stable oral glucocorticoids within 6 weeks of planned randomization
Participants taking non-steroidal anti-inflammatory drugs (NSAIDs) intermittently (up to 2-3 times weekly) for short-term relief of pain and participants on regular NSAID use (on stable dose for ≥ 4 weeks)

Exclusion Criteria:

Parenteral glucocorticoids administration (intramuscular, IV) of ≥50 mg within 6 weeks or less than or equal to (≤) 50 milligrams (mg) within 4 weeks prior to planned randomization, or scheduled parenteral administrations during the study
Joint(s) injected with intra-articular glucocorticoids or hyaluronic acid within 6 weeks prior to planned randomization
Active inflammatory diseases of the joints not related to RA
Systemic autoimmune disease other than RA
Juvenile idiopathic arthritis or juvenile RA and/or RA developed before the age of 16
Active fibromyalgia that makes appropriate assessment of RA disease activity challenging in the opinion of the Investigator
RA participants functional status class IV according to the ACR 1991 criteria
Participants with severe chronic or recurrent viral, bacterial, parasitic, or fungal infections
History of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
Any identified confirmed congenital or acquired immunodeficiency
Abnormal laboratory values and liver function test
Myocardial infarction within less than 6 months prior to participation in the study
Severe central or peripheral nervous system diseases

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pinnacle Research Group; Llc, Central		Anniston	Alabama	36207	United States
Arizona Arthritis & Rheumatology Associates, P.C.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	PoC Placebo to Extension Period Analysis RO7123520	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56. Participants from this group that continued to the Extension Period Analysis period were assigned RO7123520 + pre-trial anti-TNF-alpha and MTX at either 360 or 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 28, 2018

Arm/Group Information

ID	Title	Description
BG000	PoC Placebo to Extension Period Analysis RO7123520	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56. Participants from this group that continued to the Extension Period Analysis period were assigned RO7123520 + pre-trial anti-TNF-alpha and MTX at either 360 or 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).
BG001	RO70123520 360 or 810 mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56. Participants continuing to the Extension Period Analysis period received 360 or 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Proof of Concept participants

The proof of concept groups included 37 participants receiving placebo treatment and 72 participants receiving 810 mg/dose of RO7123520.

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG00048.6 OG00160.0 OG00266.7 OG003

Primary

Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12

The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.

The efficacy population included all randomized participants. Overall study = up to 32 weeks per participant. PoC = Weeks 1-12, Extension Period Analysis = Weeks 1-20 (overall study weeks 13-32)

Posted

Number

90% Confidence Interval

Percent

Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002

Primary

Percentage of Participants With Anti-Drug Antibodies

This outcome measure only includes the immunogenicity population, which was the PoC 810 mg dose group. These participants had at least 1 pre-dose ADA assessment.

Posted

Number

Percent

Baseline

ID	Title	Description
OG000	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.

Units	Counts
Participants	OG00069

Primary

Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans

The safety population included all participants who received at least one dose of study medication.

Posted

Mean

Standard Deviation

g/cm^2

Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).
OG003	Extension Period Analysis: RO70123520 810mg/Dose

Secondary

Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12

The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity.

The efficacy population included all randomized participants.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).

Secondary

Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12

The DAS28 is a combined index for measuring disease activity in RA; the "28" refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.

The efficacy population included all randomized participants.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).

Secondary

Percentage of Participants Achieving DAS28 Remission at Week 12

The efficacy population included all randomized participants.

Posted

Number

Percent

Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).

Secondary

Percentage of Participants Achieving CDAI Remission at Week 12

The efficacy population included all randomized participants.

Posted

Number

Percent

Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).

Secondary

Percentage of Participants Achieving ACR20 Response at Week 12

The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.

The efficacy population included all randomized participants.

Posted

Number

90% Confidence Interval

Percent

Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose

Secondary

Percentage of Participants Achieving ACR70 Response at Week 12

The ACR70 is a composite measure defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.

The efficacy population included all randomized participants.

Posted

Number

90% Confidence Interval

Percent

Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose

Secondary

Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12

The SDAI consists of 5 parameters used to assess RA disease activity: 28-joint count assessments of tenderness and swelling, participant and investigator global assessments, and CRP levels. A composite score is produced, with remission defined as an SDAI of <3.3, low disease activity as ≤11, moderate disease activity as ≤26 and high disease activity as >26.

The efficacy population included all randomized participants.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).

Secondary

Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

The HAQ-DI is a 20-item, validated questionnaire used to assess difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming (2 items), Hygiene (3 items), Arising (2 items), Reach (2 items), Eating (3 items), Grip (3 items), Walking (2 items), Common Daily Activities (3 items). The questions assess usual abilities ranging from 0 "without any difficulty" to 3 "unable to do." A lower HAQ-DI score indicates better quality of life. Subscale scores are combined and the mean value is reported for each arm per timepoint.

The efficacy population included all randomized participants.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002

Secondary

Serum RO7123520 Concentration

All enrolled participants were included in the PK population. No PK analysis was performed due to an insufficient number of available participant samples for processing.

Posted

Pre-dose (0 hour), 1 hour post infusion (duration of infusion: approximately 1 hour) on Days 1, 14, 28, 56; Pre-dose (0 hour) on Days 84, 112

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).
OG003	Extension Period Analysis: RO70123520 810mg/Dose

Secondary

Synovial Fluid RO7123520 Concentration

All enrolled participants were included in the PK population. No PK analysis was performed due to an insufficient number of available participant samples for processing.

Posted

Pre-dose (0 hour) on Days 1, 84

ID	Title	Description
OG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.
OG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.
OG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).
OG003	Extension Period Analysis: RO70123520 810mg/Dose	Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.	37	1	37	10	37
EG001	Proof of Concept: RO7123520 810mg/Dose	In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.	70	1	70	10	70
EG002	Extension Period Analysis: RO7123520 360mg/Dose	Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).	9	1	9	6	9
EG003	Extension Period Analysis: RO70123520 810mg/Dose	Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).	97	0	97	17	97

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthritis bacterial	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected70 at risk EG0020 affected9 at risk EG0030 affected97 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected70 at risk EG0020 affected9 at risk EG003
Metastatic squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Tonsil cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG0030 affected97 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Chronic tonsillitis	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Folliculitis	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Laryngitis	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0020 affected9 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA v21.1	Non-systematic Assessment	EG0001 affected37 at risk EG0014 affected70 at risk EG0020 affected9 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0014 affected70 at risk EG0020 affected9 at risk EG003
Headache	Nervous system disorders	MedDRA v21.1	Non-systematic Assessment	EG0003 affected37 at risk EG0011 affected70 at risk EG0021 affected9 at risk EG003
Dizziness	Nervous system disorders	MedDRA v21.1	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected70 at risk EG0021 affected9 at risk EG003
Pyrexia	General disorders	MedDRA v21.1	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected70 at risk EG0020 affected9 at risk EG003
C-reactive protein increased	Investigations	MedDRA v21.1	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected70 at risk EG0020 affected9 at risk EG003
Computerised tomogram abnormal	Investigations	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Neck mass	Musculoskeletal and connective tissue disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected70 at risk EG0021 affected9 at risk EG003

Certain Agreements

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds