Fibromyalgia
Conditions
Keywords
Fibromyalgia
Brief summary
The purpose of this study study is to determine whether TD-9855 is effective in treating patients with fibromyalgia.
Interventions
DRUGTD-9855 Group 1
DRUGTD-9855 Group 2
DRUGPlacebo
Sponsors
Theravance Biopharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* • American College of Rheumatology (ACR) Diagnostic Criteria for Fibromyalgia (FM) * Informed consent * 18 to 65 years of age * Discontinue therapy with adrenergic-acting drugs, and certain other medications * Only acetaminophen or NSAID as rescue pain medication * No narcotic pain meds or benzodiazepines * Only non-benzodiazepines as rescue hypnotics
Exclusion criteria
* Any current psychiatric disorder, lifetime bipolar disorder, severe comorbid Axis II disorder, mental retardation, etc, as assessed by Mini International Neuropsychiatric Interview (MINI) * Major depression at screening by MINI when unable to be washed out of MDD meds (investigator or provider's judgment) * Risk of suicide (investigator opinion and/or C-SSRS) * Recent history of substance or alcohol abuse * BMI \<18 or ≥45 * Concurrent disease; pain for diagnosed illness other than FM; non-compliance; history of seizures; pheochromocytoma; glaucoma; CV disease; orthostatic hypotension or orthostatic tachycardia; untreated sleep apnea * Abnormal lab values (liver, kidney, thyroid, and others)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Pain Score Based on the Mean of the Last 7 Daily Pain Numeric Rating Scale (NRS) Scores From the Daily Pain Diaries | Baseline and Week 6 | Pain NRS score is based on an 11-point scale where 0 represents no pain and 10 represents the worst possible pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fibromyalgia Impact Questionnaire (FIQ) | Day 43 (End of study treatment) | FIQ score is based on the total score from 0 to 100 gained from 10 questions, where a lower total score represents less impact from fibromyalgia. |
| Patient Global Impression of Change (PGIC) | Day 43 (End of study treatment) | PGIC score is based on a 7-category scale where a score of 1 indicates the participant's condition is very much improved, and a score of 7 indicates the participant's condition is very much worse. |
Countries
United States
Participant flow
Recruitment details
392 participants were enrolled across 53 study sites in the United States.
Pre-assignment details
392 participants were enrolled, but 9 participants were not treated with the study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants will be administered a placebo once daily for 6 weeks. | 130 |
| TD-9855 Group 1 Participants will be administered TD-9855 at an initial dose of 2.5 mg once daily for 1 week, before increasing the dose to 5 mg once daily for the following 5 weeks. Participants who are unable to tolerate the initial dose level will be discontinued from further dosing and will be considered to have withdrawn prematurely from the study. | 131 |
| TD-9855 Group 2 Participants will be administered TD-9855 at an initial dose of 10 mg once daily for 1 week, before increasing the dose to 20 mg once daily for the following 5 weeks. Participants who are unable to tolerate the initial dose level will be discontinued from further dosing and will be considered to have withdrawn prematurely from the study. | 131 |
| Total | 392 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 14 | 9 |
| Overall Study | Lost to Follow-up | 2 | 2 | 3 |
| Overall Study | Other | 4 | 4 | 6 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 4 | 6 |
| Overall Study | Withdrawal by Subject | 12 | 10 | 11 |
Baseline characteristics
| Characteristic | Total | TD-9855 Group 1 | TD-9855 Group 2 | Placebo |
|---|---|---|---|---|
| Age, Continuous | 45.7 years | 48.0 years | 43.2 years | 45.8 years |
| Age, Customized Age (years) 18 - 45 Years of Age | 179 Participants | 51 Participants | 73 Participants | 55 Participants |
| Age, Customized Age (years) 46 - 65 Years of Age | 213 Participants | 80 Participants | 58 Participants | 75 Participants |
| Body Mass Index | 30.2 kg/m^2 STANDARD_DEVIATION 5.89 | 30.7 kg/m^2 STANDARD_DEVIATION 5.74 | 29.3 kg/m^2 STANDARD_DEVIATION 5.59 | 30.7 kg/m^2 STANDARD_DEVIATION 6.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 57 Participants | 16 Participants | 19 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 333 Participants | 115 Participants | 112 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Height | 164.0 cm STANDARD_DEVIATION 7.69 | 164.5 cm STANDARD_DEVIATION 7.65 | 164.0 cm STANDARD_DEVIATION 8.49 | 163.3 cm STANDARD_DEVIATION 6.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants | 18 Participants | 20 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 6 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 324 Participants | 107 Participants | 107 Participants | 110 Participants |
| Region of Enrollment United States | 392 participants | 131 participants | 131 participants | 130 participants |
| Sex: Female, Male Female | 369 Participants | 123 Participants | 123 Participants | 123 Participants |
| Sex: Female, Male Male | 23 Participants | 8 Participants | 8 Participants | 7 Participants |
| Weight | 81.4 kg STANDARD_DEVIATION 17.57 | 83.2 kg STANDARD_DEVIATION 17.68 | 79.0 kg STANDARD_DEVIATION 17.27 | 81.9 kg STANDARD_DEVIATION 17.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 128 | 0 / 127 | 0 / 128 |
| other Total, other adverse events | 71 / 128 | 78 / 127 | 90 / 128 |
| serious Total, serious adverse events | 0 / 128 | 1 / 127 | 1 / 128 |
Outcome results
Primary
Percentage Change in Pain Score Based on the Mean of the Last 7 Daily Pain Numeric Rating Scale (NRS) Scores From the Daily Pain Diaries
Pain NRS score is based on an 11-point scale where 0 represents no pain and 10 represents the worst possible pain.
Time frame: Baseline and Week 6
Population: Only participants with available data were used for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in Pain Score Based on the Mean of the Last 7 Daily Pain Numeric Rating Scale (NRS) Scores From the Daily Pain Diaries | -0.9 percentage change | Standard Error 0.17 |
| TD-9855 Group 1 | Percentage Change in Pain Score Based on the Mean of the Last 7 Daily Pain Numeric Rating Scale (NRS) Scores From the Daily Pain Diaries | -1.2 percentage change | Standard Error 0.18 |
| TD-9855 Group 2 | Percentage Change in Pain Score Based on the Mean of the Last 7 Daily Pain Numeric Rating Scale (NRS) Scores From the Daily Pain Diaries | -1.4 percentage change | Standard Error 0.17 |
p-value: 0.1683ANCOVA
p-value: 0.0277ANCOVA
Secondary
Fibromyalgia Impact Questionnaire (FIQ)
FIQ score is based on the total score from 0 to 100 gained from 10 questions, where a lower total score represents less impact from fibromyalgia.
Time frame: Day 43 (End of study treatment)
Population: Only participants with available data were used for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Fibromyalgia Impact Questionnaire (FIQ) | 44.0 score on a scale | Standard Deviation 1.75 |
| TD-9855 Group 1 | Fibromyalgia Impact Questionnaire (FIQ) | 42.4 score on a scale | Standard Deviation 1.75 |
| TD-9855 Group 2 | Fibromyalgia Impact Questionnaire (FIQ) | 38.2 score on a scale | Standard Deviation 1.75 |
p-value: 0.2637ANCOVA
p-value: 0.0097ANCOVA
Secondary
Patient Global Impression of Change (PGIC)
PGIC score is based on a 7-category scale where a score of 1 indicates the participant's condition is very much improved, and a score of 7 indicates the participant's condition is very much worse.
Time frame: Day 43 (End of study treatment)
Population: Only participants with available data were used for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient Global Impression of Change (PGIC) | 3.2 score on a scale | Standard Error 0.11 |
| TD-9855 Group 1 | Patient Global Impression of Change (PGIC) | 2.9 score on a scale | Standard Error 0.11 |
| TD-9855 Group 2 | Patient Global Impression of Change (PGIC) | 2.8 score on a scale | Standard Error 0.11 |
p-value: 0.0639ANCOVA
p-value: 0.007ANCOVA