Trial Outcomes & Findings for A Study in Rheumatoid Arthritis (RA) Patients to Compare Two Formulations of Adalimumab for Pharmacokinetic, Pharmacodynamic and Safety (NCT NCT01712178)

NCT ID: NCT01712178

Last Updated: 2014-06-11

Results Overview

Blood samples for adalimumab analysis were collected by venipuncture and serum concentrations of adalimumab were determined using a validated enzyme-linked immunoadsorbent assay (ELISA) method.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: Measured at Weeks 12 and 24
• Results posted on: 2014-06-11

Participant Flow

Participant milestones

Measure	New Formulation of Adalimumab 40 mg Every Other Week New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Overall Study STARTED	50	50
Overall Study COMPLETED	49	47
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Measure	New Formulation of Adalimumab 40 mg Every Other Week New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Overall Study Withdrew consent due to an adverse event	1	1
Overall Study Serious adverse event/withdrew consent	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

A Study in Rheumatoid Arthritis (RA) Patients to Compare Two Formulations of Adalimumab for Pharmacokinetic, Pharmacodynamic and Safety

Baseline characteristics by cohort

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week	Total n=100 Participants Total of all reporting groups
Age, Continuous	55.5 years STANDARD_DEVIATION 11.0 • n=5 Participants	53.0 years STANDARD_DEVIATION 12.3 • n=7 Participants	54.3 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	41 Participants n=7 Participants	82 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at Weeks 12 and 24

Population: Data from participants receiving the new formulation of adalimumab were analyzed for 46 and 47 participants, respectively, at weeks 12 and 24. Data for the participants receiving the current formulation of adalimumab were analyzed for 43 participants at week 12 and 41 participants at week 24.

Blood samples for adalimumab analysis were collected by venipuncture and serum concentrations of adalimumab were determined using a validated enzyme-linked immunoadsorbent assay (ELISA) method.

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=47 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=43 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Serum Concentrations of Adalimumab at Weeks 12 and 24 Week 12: n= 46 (new), n=43 (current)	5.72 µg/mL Standard Deviation 4.49	6.23 µg/mL Standard Deviation 4.29
Serum Concentrations of Adalimumab at Weeks 12 and 24 Week 24: n= 47 (new), n=41 (current)	5.95 µg/mL Standard Deviation 5.13	6.17 µg/mL Standard Deviation 4.50

PRIMARY outcome

Timeframe: Measured at Weeks 12 and 24

Population: All available data were included. If a subject did not have a value for a given time of evaluation, but did have a value at times previous to this after the study drug treatment began, the last available value was used to replace the missing value.

The Disease Activity Score (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Mean Disease Activity Scores (DAS28) at Weeks 12 and 24 Week 12	3.78 units on a scale Standard Error 0.147	3.82 units on a scale Standard Error 0.148
Mean Disease Activity Scores (DAS28) at Weeks 12 and 24 Week 24	3.54 units on a scale Standard Error 0.152	3.46 units on a scale Standard Error 0.153

SECONDARY outcome

Timeframe: Measured at Weeks 12 and 24

Population: All available data were included. If a subject did not have a value for a given time of evaluation, but did have a value at times previous to this after the study drug treatment began, the last available value was used to replace the missing value.

American College of Rheumatology 20% (ACR20) response. A participant is a responder if the following 3 criteria for improvement from baseline are met:

• ≥ 20% improvement in tender joint count;
• ≥ 20% improvement in swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:

• Physician global assessment of disease activity
• Patient global assessment of disease activity
• Patient assessment of pain
• Disability Index of the Health Assessment Questionnaire
• CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 12 and 24 Week 12	62.0 percentage of participants	68.0 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 12 and 24 Week 24	68.0 percentage of participants	68.0 percentage of participants

SECONDARY outcome

Timeframe: Measured at Weeks 12 and 24

Population: All available data were included. If a subject did not have a value for a given time of evaluation, but did have a value at times previous to this after the study drug treatment began, the last available value was used to replace the missing value.

American College of Rheumatology 50% (ACR50) response. A participant is a responder if the following 3 criteria for improvement from baseline are met:

• ≥ 50% improvement in tender joint count;
• ≥ 50% improvement in swollen joint count; and
• ≥ 50% improvement in at least 3 of the 5 following parameters:

• Physician global assessment of disease activity
• Patient global assessment of disease activity
• Patient assessment of pain
• Disability Index of the Health Assessment Questionnaire
• CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 12 and 24 Week 12	36.0 percentage of participants	40.0 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 12 and 24 Week 24	48.0 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Measured at Weeks 12 and 24

Population: All available data were included. If a subject did not have a value for a given time of evaluation, but did have a value at times previous to this after the study drug treatment began, the last available value was used to replace the missing value.

The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is ≥0.22. HAQ remission indicating normal physical function is defined by HAQ-DI < 0.5.

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Mean Health Assessment Questionnaire (HAQ-DI) Scores at Weeks 12 and 24 Week 12	1.10 units on a scale Standard Error 0.075	1.02 units on a scale Standard Error 0.076
Mean Health Assessment Questionnaire (HAQ-DI) Scores at Weeks 12 and 24 Week 24	1.01 units on a scale Standard Error 0.082	0.97 units on a scale Standard Error 0.083

SECONDARY outcome

Timeframe: Measured at Weeks 12 and 24

Population: All available data were included. If a subject did not have a value for a given time of evaluation, but did have a value at times previous to this after the study drug treatment began, the last available value was used to replace the missing value.

The Short Form 36 (SF-36) determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary score (PCS) of the SF-36. Items 5-8 primarily contribute to the mental component summary score (MCS) of the SF-36. Scores on each item are summed and averaged (range = 0 (maximum disability) - 100 (no disability). The standard recall period is four weeks.

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=49 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Mean Short Form-36 (SF-36) Physical Component Summary Scores and Mental Component Summary Scores at Weeks 12 and 24 PCS score- Week 12	38.88 units on a scale Standard Error 0.957	39.08 units on a scale Standard Error 0.974
Mean Short Form-36 (SF-36) Physical Component Summary Scores and Mental Component Summary Scores at Weeks 12 and 24 PCS score- Week 24	39.38 units on a scale Standard Error 1.044	39.94 units on a scale Standard Error 1.022
Mean Short Form-36 (SF-36) Physical Component Summary Scores and Mental Component Summary Scores at Weeks 12 and 24 MCS score- Week 12	44.78 units on a scale Standard Error 1.172	42.78 units on a scale Standard Error 1.192
Mean Short Form-36 (SF-36) Physical Component Summary Scores and Mental Component Summary Scores at Weeks 12 and 24 MCS score- Week 24	43.16 units on a scale Standard Error 1.246	45.46 units on a scale Standard Error 1.267

SECONDARY outcome

Timeframe: Measured through Week 24

Percentage of participants with anti-adalimumab antibody

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Percentage of Participants Positive for Anti-adalimumab Antibody	14 Percentage of participants	16 Percentage of participants

SECONDARY outcome

Timeframe: From time of informed consent to 70 days following the last dose of study drug

An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. See the Reported Adverse Events Section for more details.

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Number of Participants With Adverse Events	31 participants	34 participants

SECONDARY outcome

Timeframe: Immediately after injections on Day 1

The Visual Analogue Scale (VAS) consisted of a horizontal 100 mm line, with 0 representing "no pain" and 100 representing "worst possible pain". Participants placed a mark on the line representing their current level of pain immediately after injections on Day 1 of the study.

Outcome measures

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=49 Participants New formulation adalimumab 40 mg every other week Adalimumab, new formulation: New formulation adalimumab 40 mg every other week	Current Formulation Adalimumab 40 mg Every Other Week n=50 Participants Current formulation adalimumab 40 mg every other week Adalimumab, current formulation: Current formulation adalimumab 40 mg every other week
Mean Injection Site Pain on a Visual Analogue Scale (VAS)	14.4 Millimeters Standard Deviation 22.6	35.9 Millimeters Standard Deviation 29.2

Adverse Events

New Formulation of Adalimumab 40 mg Every Other Week

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Current Formulation Adalimumab 40 mg Every Other Week

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 participants at risk	Current Formulation Adalimumab 40 mg Every Other Week n=50 participants at risk
Injury, poisoning and procedural complications THORACIC VERTEBRAL FRACTURE	0.00% 0/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	2.0% 1/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TRANSITIONAL CELL CARCINOMA	0.00% 0/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	2.0% 1/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.

Other adverse events

Measure	New Formulation of Adalimumab 40 mg Every Other Week n=50 participants at risk	Current Formulation Adalimumab 40 mg Every Other Week n=50 participants at risk
Gastrointestinal disorders DYSPEPSIA	6.0% 3/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	2.0% 1/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Gastrointestinal disorders NAUSEA	8.0% 4/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	0.00% 0/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
General disorders INJECTION SITE REACTION	6.0% 3/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	0.00% 0/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Infections and infestations CYSTITIS	8.0% 4/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	4.0% 2/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Infections and infestations NASOPHARYNGITIS	10.0% 5/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	12.0% 6/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Infections and infestations SINUSITIS	6.0% 3/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	2.0% 1/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	8.0% 4/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	8.0% 4/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Musculoskeletal and connective tissue disorders RHEUMATOID ARTHRITIS	6.0% 3/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	8.0% 4/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.
Respiratory, thoracic and mediastinal disorders COUGH	6.0% 3/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.	2.0% 1/50 • Adverse events were collected from the time of study drug administration until 70 days following the last dose. Serious adverse events were collected from the time the participant signed the informed consent.

Additional Information

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