NCT03783910已完成2 期
Cross-over Multiple Dose Study Assessing the Analgesic Efficacy and Safety of Oral GRT9906 Compared to Placebo in Subjects With Primary Fibromyalgia Syndrome
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 6
- 主要终点
- Average Pain Intensity over last 3 days of treatment period
研究概览
简要总结
The study was performed in participants suffering from fibromyalgia and investigated efficacy after treatment with several doses of GRT9906 versus placebo. Furthermore, it was to be found out if treatment with GRT9906 was safe and well-tolerated.
详细描述
This Phase 2 study had a randomized, multi-center, double-blind, placebo-controlled, crossover, multiple-administration design.
The objectives of the study were the following:
- To assess the multiple-dose analgesic efficacy and safety of an oral prolonged-release (PR) tablet formulation of GRT9906 at daily doses between 80 and 240 milligrams (mg) in comparison to placebo in participants with moderate to severe pain due to primary fibromyalgia syndrome (FMS).
- To compare the tolerability of multiple-dose GRT9906 PR to placebo in participants with primary FMS.
- To generate data that could be used, in combination with data from other studies, to explore the population pharmacokinetic analysis and pharmacokinetic/pharmacodynamic (PK/PD) properties of GRT9906 PR.
The study consisted of 5 phases:
- Enrollment including tapering, if necessary, and washout (at least 1 week) of previous medication.
- First treatment period with 1-week titration and 5-weeks dosing on participant's last well-tolerated titration dosage.
- Interim washout period of at least 1 week.
- Second treatment period with 1-week titration and 5-weeks dosing on participant's last well-tolerated titration dosage.
- Final washout period of at least 1 week, terminated by a Follow-up Visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ambulatory participants of any ethnic group, aged 18 to 75 years inclusive at enrollment.
- •Primary fibromyalgia syndrome (FMS) diagnosed according to the American College of Rheumatology (ACR) 1990 criteria, persistent for at least 6 months.
- •Average Pain Intensity of FMS pain over the last 3 days before randomization visit must be at least 4 points, using 11-point numerical rating scale (NRS).
- •Negative urine test for drugs of abuse at the Day 1 visit of each treatment period.
- •Women of childbearing potential must use an acceptable method of contraception (i.e., double barrier, hormonal or intra-uterine device method) during the study period and have a negative urine pregnancy test at the Enrollment Visit and at the Day 1 visit of each treatment period.
- •Compliance with use and completion of assessments by means of electronic diaries; 80 percent of entries must be available for the week before randomization.
- •Written informed consent for study participation given.
排除标准
- •Participation in another study of IMPs or devices parallel to, or less than 1 month prior to enrollment, or previous participation in this study.
- •Known to or suspected of not being able to comply with the study protocol and the use of the IMPs.
- •Not able to communicate meaningfully with the Investigator and staff.
- •Evidence or history of alcohol, medication or drug dependency during the past 12 months. History of opiate dependency at any point in life.
- •Evidence or history of neurotic personality, psychiatric illness including anxiety disorder, severe senile dementia, Alzheimer's disease, history of seizures or pre-existing conditions that lower seizure threshold (e.g., head trauma), or suicide risk.
- •Current depression needing treatment with antidepressants.
- •Currently or previously diagnosed with malignancies except basal cell carcinoma; poor medical status (e.g., New York Heart Association [NYHA] class equal to or above 3; Child classification for hepatic impairment above A [Pugh et al. 1973]; decompensated chronic obstructive pulmonary disease) or, at the discretion of the Investigator, clinical signs that raise concerns about participant's suitability for the study.
- •Creatinine higher than 1.5-times of upper limit of normal (ULN) range.
- •Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than twice the ULN range.
- •Any chronic disease (e.g., hepatic, renal and/or gastrointestinal) that might affect drug absorption, metabolism or excretion.
- •Nursing mother.
- •Causes of chronic pain other than FMS and mild osteoarthritis of the hand.
- •Proven rheumatoid disease with positive rheumatoid factor or antinuclear antibody (ANA) at screening.
- •History of marked repolarization abnormality (e.g., suspicion of or definite congenital long QT syndrome).
- •QT values of: corrected QT Bazett (QTcB) females equal to or above 450 milliseconds (ms), QTcB males equal to or above 430 ms, uncorrected QT equal to or above 500 ms at Enrollment Visit.
- •Definite or suspected allergy or hypersensitivity to drugs having a similar mechanism of action as IMP. Known contraindications/hyper-sensitivity to opioids, acetaminophen or zolpidem.
- •Intolerance to galactose.
- •Dysphagia or difficulty swallowing tablets or capsules.
- •Blood donation (above 100 milliliters) or comparable blood losses within 3 months prior to the start of this study.
- •History of Gilbert's Disease.
- •Use of anti-epileptic drugs, chloramphenicol, rifampicin, or zidovudine.
- •Use of fentanyl transdermal system, buprenorphine sublingual or transdermal system, cyclooxygenase (COX) 2 inhibitors with a half-life of more than 35 hours, equal to or less than 7 days prior to enrollment.
- •Use of serotonergic drugs, drugs with the potential to prolong QT interval, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) substrates, antiparkinson drugs, monoamineoxidase (MAO)-inhibitors, neuroleptics, or other drugs that may lower the seizure threshold, within less than 5 half-life times prior to randomization.
- •Use of any analgesics (including non-steroidal anti-inflammatory drugs [NSAIDs] and COX2 inhibitors) others than investigational medicinal products and acetaminophen as rescue medication as well as sedative hypnotics (with the exception of 5 milligrams zolpidem for a maximum of 3 days per week) within less than 5 half-life times prior to randomization.
- •Physical therapy and/or other non-pharmacological pain therapy (e.g., acupuncture, transcutaneous electrical nerve stimulation [TENS]) after Enrollment Visit if not started at least 6 months before enrollment.
- •Systemic (parenteral and/or oral) steroids during previous month.
- •Tender point injections (with local anesthetics or others) during the previous month.
- •Participants currently involved in litigation regarding FMS, pending or active disability-compensation claim.
研究组 & 干预措施
GRT9906
Experimental
Participants received 80-240 mg of GRT9906 oral for up to 6 weeks (1 week of titration, 5 weeks of maintenance treatment).
Participants started with 40 mg of GRT9906 on the first and 80 mg (40 mg twice daily) on the second day. They could increase the dose every day by 1 tablet (i.e., GRT9906 40 mg), up to a maximum daily dose of 240 mg (120 mg twice daily). Participants experiencing adverse events could reduce the dose to the next lower, better tolerated daily dose (but not lower than 80 mg [40 mg twice daily]). By Day 8, every participant had reached their optimal daily dose and was asked to continue on the identified dosing regimen for the following 5 weeks.
干预措施: GRT9906 (Drug)
Placebo
Placebo Comparator
Participants received Placebo (2-6 tablets daily) oral for up to 6 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Average Pain Intensity over last 3 days of treatment period
时间窗: Last 3 days of treatment period
Participants recorded their daily current pain intensity in an electronic diary from the Enrollment Visit until the day of the last visit in the second treatment period using an 11-point Numerical Rating scale (NRS) ranging from 0 = no pain to 10 = pain as bad as you can imagine. Each treatment period lasted for 6 weeks. For the primary endpoint, the average daily current pain intensity over the last 3 days prior to the last visit per treatment period was calculated.
次要结局
- Changes from baseline/period baseline in Average Pain Intensity over last 3 days per treatment period(At baseline, at period baseline, and for last 3 days of each treatment period)
- Fibromyalgia Impact Questionnaire (FIQ)(At Enrollment Visit (Visit 1), on Day 1, Day 22, and Day 42 per treatment period, and at Final Visit (14 days after last dose in treatment period 2))
- Average Pain Threshold (APT)(At Enrollment Visit (Visit 1), on Day 1, Day 22, and Day 42 per treatment period, and at Final Visit (14 days after last dose in treatment period 2))
- Morning Stiffness Questionnaire (MSQ)(At Enrollment Visit (Visit 1), on Day 1, Day 22, and Day 42 per treatment period, and at Final Visit (14 days after last dose in treatment period 2))
- 30 percent reduction in pain based on Average Pain Intensity (API)(Prior to the last visit in each treatment period (Day 42))
- 50 percent reduction in pain based on Average Pain Intensity (API)(Prior to the last visit in each treatment period (Day 42))
- Subject's Global Assessment of the investigational medicinal product (IMP)(On Day 42 of each treatment period)
- Number needed to treat (NNT) for 50 percent reduction in pain(Prior to the last visit in each treatment period (Day 42))
- Patient's Global Impression of Change (PGIC)(On Day 42 of each treatment period)
- Mean daily number of rescue medication tablets taken(From Day 1 to Day 42 over each treatment period)
- Total amount of rescue medication taken(From Day 1 to Day 42 over each treatment period)
- Average Pain Intensity after initial washout and over Weeks 1 to 6 per treatment period(Last 3 days of the initial washout period; Week 1, 2, 3, 4, 5 and 6 per treatment period)
- Major Depression Inventory (MDI)(At Enrollment Visit (Visit 1), on Day 1, Day 22, and Day 42 per treatment period, and at Final Visit (14 days after last dose in treatment period 2))
- Number needed to treat (NNT) for 30 percent reduction in pain(Prior to the last visit in each treatment period (Day 42))
- Quality of sleep using the Sleep Problem Scale (SPS)(At Visit 1 and on Day 42 of each treatment period)
- Tender Point Index (TPI)(At Enrollment Visit (Visit 1), on Day 1, Day 22, and Day 42 per treatment period, and at Final Visit (14 days after last dose in treatment period 2))
- Change from baseline in Sleep Problem Scale (SPS) total score(At Enrollment Visit (Visit 1) and on Day 42 per treatment period)
- Investigator's Global Assessment of the investigational medicinal product (IMP)(On Day 42 of each treatment period)
- Clinical Opiate Withdrawal Scale (COWS)(At Visit 1 and Day 45 (2-4 days after last day of intake of IMP per treatment period))
研究者
研究点 (6)
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