Fibromyalgia
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of recombinant human growth hormone (r-hGH) treatment in severe fibromyalgia subjects with growth axis dysfunction.
Interventions
DRUGPlacebo and Saizen®
Placebo matched to Saizen® will be administered for the first 6 months followed by treatment with Saizen® (Somatropin) 0.006 mg/kg subcutaneously daily for next 6 months. Saizen® dose will be titrated (an increase of 0.2 milligram per day) if the increase in insulin-like growth factor 1 (IGF-1) is less than 50 percent of the baseline value. Dose titrations will be made at Month 7 and 9.
DRUGSaizen®
Saizen® (Somatropin) 0.006 milligram per kilogram (mg/kg) will be administered subcutaneously daily for 12 months. Dose will be titrated (an increase of 0.2 milligram per day) if the increase in insulin-like growth factor 1 (IGF-1) is less than 50 percent of the baseline value. Dose titrations will be made at Month 1, 3, 7 and 9.
Sponsors
Merck, S.L., Spain
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women aged greater than or equal (\>=) 18 years * Fibromyalgia diagnosed at least one year before * History of generalized pain and at least 16 positive tender points (1990 American College of Rheumatology \[ACR\] criteria) * Body Mass Index (BMI) less than or equal to(=\<) 32 * Normal GH stimulation test (insulin) * Stable (\>= 3 months unchanged) standard treatment with amitriptyline (10-50 milligram per day \[mg/day\]) plus selective serotonin reuptake inhibitor (10-40 mg/day) plus tramadol (25-400 mg/day) * Active rehabilitation program during the previous year (at least 30 minutes/day) * Fibromyalgia Impact Questionnaire (FIQ) score \>=75 * IGF-1 serum level =\< 150 nanogram/milliliter (ng/mL) otherwise =\< 2 SD of the local lab normality) * Normal response to IGF-1 generation test * Chronic Fatigue Symptoms (Multidimensional Assessment of Fatigue \[MAF\]) * Effective anti-conception * Willingness to comply with the protocol * Written Informed consent
Exclusion criteria
* Major psychiatric condition * Rheumatic disease, including systemic lupus erythematosus (SLE) * Previous or current malignancies, active or inactive * Clinical history intracranial space occupying lesion * Reactive or secondary (rheumatoid arthritis \[RA\], osteoarthritis) fibromyalgia syndrome (FMS) * Antinuclear antibody (ANA) greater than or equal 1:80 * Abnormal Creatine phosphokinase (CPK) or aldolase serum levels * Not controlled thyroid disease in the last 3 months (free Thyroxine \[T4\] and Thyrotrophin-stimulating hormone \[TSH\] serum levels) * Diabetes mellitus * Adrenal gland disease (any abnormal cortisolemia, will be confirmed by 24-hour cortisoluria) * Pregnancy or breast feeding * Known to be hypersensitive to somatotropin or any of the excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Less Than 11 Tender Points at Month 6 | Month 6 | The musculoskeletal component in form of pain on palpation in at least 11 of 18 tender point sites is required to fulfill the American College of Rheumatology (ACR) criteria for fibromyalgia syndrome, An important response is considered when the number of tender points falls below 11 since it is the threshold for fibromyalgia diagnosis. |
| Percentage of Participants With Less Than 11 Tender Points at Month 12 | Month 12 | The musculoskeletal component in form of pain on palpation in at least 11 of 18 tender point sites is required to fulfill the ACR criteria for fibromyalgia syndrome, An important response is considered when the number of tender points falls below 11 since it is the threshold for fibromyalgia diagnosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EuroQol 5-Dimensions (EQ-5D) Total Score | Baseline, Month 1, 3, 6, 7, 9 and 12 | EuroQol 5-Dimensions (EQ-5D) questionnaire is a measure of health status and quality of life (QoL). The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Score range for each item is 0 to 3, with 3 being the most severe. Total score range is 0 to 15. Lower scores represent a better QoL. |
| Fibromyalgia Impact Questionnaire (FIQ) Total Score | Baseline, Month 1, 3, 6, 7, 9 and 12 | Fibromyalgia Impact Questionnaire (FIQ) is a 10-item questionnaire that measures physical impairment, well-being, missed work, pain, fatigue, rest, stiffness, anxiety, and depression. Score ranges from 0 (best result - very well) to 100 (worst result - awful). |
| Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Baseline, Month 6 and 12 | Quality of Life Assessment of GH Deficiency in Adults (QoL AGHDA) questionnaire consists of 25 items that evoke yes or no answers. A score of 1 is given to each item affirmed and these are summed to give the total score. The maximum score is 25, which represents a poor quality of life. The minimum score is 0, which represents a good quality of life. Each question has to be answered with a NO/YES and for each YES, one point is added. The more YES, the higher the score and the worse. Decrease in the positive responses is an index of improvement. So, when the percentage of positive responses on the scale decreases, it is considered a response rate. |
| Multidimensional Assessment of Fatigue (MAF) Total Score | Baseline, Month 6 and 12 | Multidimensional Assessment of Fatigue (MAF) consists of 16 questions. The score range for first 14 questions is between 0 and 10 for each question while for the last two questions it is 0 and 4 for each question. Total score range for first 14 questions is 0 to 100 and for last two questions is 0 to 8. Lower scores on the each represent the better participant's condition, whereas, higher scores indicate worsening condition. |
| Visual Analog Scale (VAS) Total Score | Baseline, Month 1, 3, 6, 7, 9 and 12 | Visual Analog Scale (VAS) is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. |
Countries
Spain
Participant flow
Recruitment details
123 subjects were enrolled of whom 113 subjects were randomised and treated.
Participants by arm
| Arm | Count |
|---|---|
| Saizen® Saizen® (Somatropin) 0.006 milligram per kilogram (mg/kg) was administered subcutaneously daily for 12 months. Saizen® dose was titrated (an increase of 0.2 milligram per day) if the increase in insulin-like growth factor 1 (IGF-1) was less than 50 percent of the baseline value. Dose titrations were made at Month 1, 3, 7 and 9. | 55 |
| Placebo + Saizen® Placebo matched to Saizen® was administered for the first 6 months followed by treatment with Saizen® (Somatropin) 0.006 mg/kg subcutaneously daily for next 6 months. Saizen® dose was titrated (an increase of 0.2 milligram per day) if the increase in IGF-1 was less than 50 percent of the baseline value. Dose titrations were made at Month 7 and 9. | 58 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Failure to show up at endpoint visits | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Saizen® | Placebo + Saizen® | Total |
|---|---|---|---|
| Age Continuous | 49.9 years STANDARD_DEVIATION 9.5 | 50.3 years STANDARD_DEVIATION 9.6 | 50.1 years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 55 Participants | 58 Participants | 113 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 55 | 51 / 58 |
| serious Total, serious adverse events | 4 / 55 | 0 / 58 |
Outcome results
Primary
Percentage of Participants With Less Than 11 Tender Points at Month 12
The musculoskeletal component in form of pain on palpation in at least 11 of 18 tender point sites is required to fulfill the ACR criteria for fibromyalgia syndrome, An important response is considered when the number of tender points falls below 11 since it is the threshold for fibromyalgia diagnosis.
Time frame: Month 12
Population: ITT population included all the participants who were randomized in the study. 'N' signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saizen® | Percentage of Participants With Less Than 11 Tender Points at Month 12 | 53 Percentage of participants |
| Placebo + Saizen® | Percentage of Participants With Less Than 11 Tender Points at Month 12 | 34 Percentage of participants |
Primary
Percentage of Participants With Less Than 11 Tender Points at Month 6
The musculoskeletal component in form of pain on palpation in at least 11 of 18 tender point sites is required to fulfill the American College of Rheumatology (ACR) criteria for fibromyalgia syndrome, An important response is considered when the number of tender points falls below 11 since it is the threshold for fibromyalgia diagnosis.
Time frame: Month 6
Population: Intention-to-treat (ITT) population included all the participants who were randomized in the study. 'N' signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saizen® | Percentage of Participants With Less Than 11 Tender Points at Month 6 | 20 Percentage of participants |
| Placebo + Saizen® | Percentage of Participants With Less Than 11 Tender Points at Month 6 | 22 Percentage of participants |
Secondary
EuroQol 5-Dimensions (EQ-5D) Total Score
EuroQol 5-Dimensions (EQ-5D) questionnaire is a measure of health status and quality of life (QoL). The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Score range for each item is 0 to 3, with 3 being the most severe. Total score range is 0 to 15. Lower scores represent a better QoL.
Time frame: Baseline, Month 1, 3, 6, 7, 9 and 12
Population: ITT population included all the participants who were randomized in the study. 'N' signifies number of participants who were evaluable for this outcome measure. 'n' signifies number of participants who were evaluable at each time-point for each arm group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 3 (n=52, 54) | 10.13 Units on a scale | Standard Deviation 0.45 |
| Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 7 (n=51, 50) | 9.63 Units on a scale | Standard Deviation 0.49 |
| Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 1 (n=52, 54) | 10.46 Units on a scale | Standard Deviation 0.45 |
| Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 9 (n=51, 50) | 9.49 Units on a scale | Standard Deviation 0.6 |
| Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 6 (n=51, 50) | 10.00 Units on a scale | Standard Deviation 0.48 |
| Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 12 (n=45, 47) | 9.09 Units on a scale | Standard Deviation 0.64 |
| Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Baseline (n=54, 57) | 11.07 Units on a scale | Standard Deviation 0.44 |
| Placebo + Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 12 (n=45, 47) | 9.94 Units on a scale | Standard Deviation 0.56 |
| Placebo + Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Baseline (n=54, 57) | 11.24 Units on a scale | Standard Deviation 0.42 |
| Placebo + Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 1 (n=52, 54) | 10.45 Units on a scale | Standard Deviation 0.42 |
| Placebo + Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 3 (n=52, 54) | 10.06 Units on a scale | Standard Deviation 0.55 |
| Placebo + Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 6 (n=51, 50) | 10.16 Units on a scale | Standard Deviation 0.56 |
| Placebo + Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 7 (n=51, 50) | 9.77 Units on a scale | Standard Deviation 0.54 |
| Placebo + Saizen® | EuroQol 5-Dimensions (EQ-5D) Total Score | Month 9 (n=51, 50) | 9.80 Units on a scale | Standard Deviation 0.5 |
Secondary
Fibromyalgia Impact Questionnaire (FIQ) Total Score
Fibromyalgia Impact Questionnaire (FIQ) is a 10-item questionnaire that measures physical impairment, well-being, missed work, pain, fatigue, rest, stiffness, anxiety, and depression. Score ranges from 0 (best result - very well) to 100 (worst result - awful).
Time frame: Baseline, Month 1, 3, 6, 7, 9 and 12
Population: ITT population included all the participants who were randomized in the study. 'N' signifies number of participants who were evaluable for this outcome measure. 'n' signifies number of participants who were evaluable at each time-point for each arm group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 3 (n=52, 54) | 72.1 Units on a scale | Standard Deviation 4.4 |
| Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 7 (n=51, 50) | 59.2 Units on a scale | Standard Deviation 5.5 |
| Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 1 (n=52, 54) | 74.6 Units on a scale | Standard Deviation 3.6 |
| Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 9 (n=51, 50) | 58.2 Units on a scale | Standard Deviation 6.4 |
| Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 6 (n=51, 50) | 65.8 Units on a scale | Standard Deviation 4.8 |
| Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 12 (n=45, 47) | 52.5 Units on a scale | Standard Deviation 6.5 |
| Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Baseline (n=54, 57) | 85.7 Units on a scale | Standard Deviation 2.3 |
| Placebo + Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 12 (n=45, 47) | 64.7 Units on a scale | Standard Deviation 6.5 |
| Placebo + Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Baseline (n=54, 57) | 86.0 Units on a scale | Standard Deviation 1.8 |
| Placebo + Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 1 (n=52, 54) | 73.3 Units on a scale | Standard Deviation 4.7 |
| Placebo + Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 3 (n=52, 54) | 66.4 Units on a scale | Standard Deviation 5.1 |
| Placebo + Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 6 (n=51, 50) | 68.4 Units on a scale | Standard Deviation 5.3 |
| Placebo + Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 7 (n=51, 50) | 65.8 Units on a scale | Standard Deviation 5.7 |
| Placebo + Saizen® | Fibromyalgia Impact Questionnaire (FIQ) Total Score | Month 9 (n=51, 50) | 65.1 Units on a scale | Standard Deviation 5.7 |
Secondary
Multidimensional Assessment of Fatigue (MAF) Total Score
Multidimensional Assessment of Fatigue (MAF) consists of 16 questions. The score range for first 14 questions is between 0 and 10 for each question while for the last two questions it is 0 and 4 for each question. Total score range for first 14 questions is 0 to 100 and for last two questions is 0 to 8. Lower scores on the each represent the better participant's condition, whereas, higher scores indicate worsening condition.
Time frame: Baseline, Month 6 and 12
Population: ITT population included all the participants who were randomized in the study. 'N' signifies number of participants who were evaluable for this outcome measure. 'n' signifies number of participants who were evaluable at each time-point for each arm group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 15 and 16 question: Month 6 (n=51, 50) | 6 Units on a scale |
| Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 1 to 14 questions: Baseline (n=54, 57) | 90 Units on a scale |
| Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 1 to 14 questions: Month 6 (n=51, 50) | 85 Units on a scale |
| Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 1 to 14 questions: Month 12 (n=45, 47) | 73 Units on a scale |
| Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 15 and 16 question: Baseline (n=54, 57) | 7 Units on a scale |
| Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 15 and 16 question: Month 12 (n=45, 47) | 5 Units on a scale |
| Placebo + Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 15 and 16 question: Baseline (n=54, 57) | 7 Units on a scale |
| Placebo + Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 15 and 16 question: Month 6 (n=51, 50) | 6 Units on a scale |
| Placebo + Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 1 to 14 questions: Month 12 (n=45, 47) | 78 Units on a scale |
| Placebo + Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 1 to 14 questions: Baseline (n=54, 57) | 83 Units on a scale |
| Placebo + Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 15 and 16 question: Month 12 (n=45, 47) | 6 Units on a scale |
| Placebo + Saizen® | Multidimensional Assessment of Fatigue (MAF) Total Score | 1 to 14 questions: Month 6 (n=51, 50) | 78 Units on a scale |
Secondary
Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale
Quality of Life Assessment of GH Deficiency in Adults (QoL AGHDA) questionnaire consists of 25 items that evoke yes or no answers. A score of 1 is given to each item affirmed and these are summed to give the total score. The maximum score is 25, which represents a poor quality of life. The minimum score is 0, which represents a good quality of life. Each question has to be answered with a NO/YES and for each YES, one point is added. The more YES, the higher the score and the worse. Decrease in the positive responses is an index of improvement. So, when the percentage of positive responses on the scale decreases, it is considered a response rate.
Time frame: Baseline, Month 6 and 12
Population: ITT population included all the participants who were randomized in the study. 'N' signifies number of participants who were evaluable for this outcome measure. 'n' signifies number of participants who were evaluable at each time-point for each arm group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saizen® | Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Baseline (n=54, 57) | 73 Percentage of participants |
| Saizen® | Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Month 6 (n=51, 50) | 70 Percentage of participants |
| Saizen® | Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Month 12 (n=45, 47) | 59 Percentage of participants |
| Placebo + Saizen® | Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Baseline (n=54, 57) | 72 Percentage of participants |
| Placebo + Saizen® | Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Month 6 (n=51, 50) | 69 Percentage of participants |
| Placebo + Saizen® | Percentage of Participants With Positive Response on Quality of Life Assessment of Growth Hormone [GH] Deficiency in Adults (QoL AGHDA) Scale | Month 12 (n=45, 47) | 70 Percentage of participants |
Secondary
Visual Analog Scale (VAS) Total Score
Visual Analog Scale (VAS) is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain.
Time frame: Baseline, Month 1, 3, 6, 7, 9 and 12
Population: ITT population included all the participants who were randomized in the study. 'N' signifies number of participants who were evaluable for this outcome measure. 'n' signifies number of participants who were evaluable at each time-point for each arm group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saizen® | Visual Analog Scale (VAS) Total Score | Month 6 (n=51, 50) | 57.6 mm | Standard Deviation 5.7 |
| Saizen® | Visual Analog Scale (VAS) Total Score | Month 7 (n=51, 50) | 54.6 mm | Standard Deviation 5.2 |
| Saizen® | Visual Analog Scale (VAS) Total Score | Baseline (n=54, 57) | 73.3 mm | Standard Deviation 3.4 |
| Saizen® | Visual Analog Scale (VAS) Total Score | Month 9 (n=51, 50) | 51.2 mm | Standard Deviation 6.7 |
| Saizen® | Visual Analog Scale (VAS) Total Score | Month 3 (n=52, 54) | 63.7 mm | Standard Deviation 5.6 |
| Saizen® | Visual Analog Scale (VAS) Total Score | Month 12 (n=45, 47) | 45.0 mm | Standard Deviation 6.9 |
| Saizen® | Visual Analog Scale (VAS) Total Score | Month 1 (n=52, 54) | 65.1 mm | Standard Deviation 4.2 |
| Placebo + Saizen® | Visual Analog Scale (VAS) Total Score | Month 12 (n=45, 47) | 60.6 mm | Standard Deviation 6 |
| Placebo + Saizen® | Visual Analog Scale (VAS) Total Score | Baseline (n=54, 57) | 74.3 mm | Standard Deviation 3.1 |
| Placebo + Saizen® | Visual Analog Scale (VAS) Total Score | Month 1 (n=52, 54) | 68.0 mm | Standard Deviation 5.7 |
| Placebo + Saizen® | Visual Analog Scale (VAS) Total Score | Month 3 (n=52, 54) | 58.4 mm | Standard Deviation 5.8 |
| Placebo + Saizen® | Visual Analog Scale (VAS) Total Score | Month 7 (n=51, 50) | 56.1 mm | Standard Deviation 6.2 |
| Placebo + Saizen® | Visual Analog Scale (VAS) Total Score | Month 9 (n=51, 50) | 60.3 mm | Standard Deviation 6.3 |
| Placebo + Saizen® | Visual Analog Scale (VAS) Total Score | Month 6 (n=51, 50) | 60.4 mm | Standard Deviation 6.6 |