Uremic Pruritus
Conditions
Brief summary
Double-blind, Placebo-controlled study to evaluate the dose-response relationship of safety, efficacy and pharmacokinetics of MA13A9 in hemodialysis patients with pruritus.
Interventions
DRUGMR13A9
Intravenous administration
DRUGPlacebo
Intravenous administration
Sponsors
Maruishi Pharmaceutical
Kissei Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Japanese with male or female aged ≥ 20 * Patient with Chronic Kidney Disease (CKD) has been on hemodialysis 3 times per week * Patient receiving treatment for itch * Patient has a baseline NRS score \> 4
Exclusion criteria
* Patient has pruritus cause other than CKD or its complications * Patients has hepatic cirrhosis * Patient has a known history of allergic reaction to opiates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean NRS Score at Week 8 of the Treatment Period | 8 weeks | The primary analysis was performed using an MMRM with change from baseline in the mean NRS score at each time point as an objective variable; treatment group, time point, and treatment group-by-time point interaction as fixed effects; baseline mean NRS score and dynamic allocation factors, presence of prior treatment with nalfurafine hydrochloride, and presence of specific signs or symptoms to be confirmed in the screening period, as covariates; and subject as a random effect. Looking back on the period between the time of awakening on the previous day of assessment and the time of awakening on the day of assessment (including sleeping hours) once daily, subjects will assess the NRS score for the most severe itching by themselves. The most severe itching within the day will be assessed in integer on a scale ranging from 0 to 10, where 0 represents no itching and 10 represents worst itching imaginable. |
Countries
Japan
Participant flow
Recruitment details
Of 311 participants who had been screened, 247 subjects were enrolled in this study and were randomly assigned to each study drugs. 225 subjects completed the study and 22 subjects discontinued the study.
Participants by arm
| Arm | Count |
|---|---|
| 0.25 μg/kg Group The study drug was injected into the venous line of the dialysis circuit at the end of each dialysis session for 8 weeks (3 times weekly, 24 times in total). The injected volume of the study drug was determined based on the subject's dry weight on the day of dosing as below.
* \< 45.0 kg: 8.75 μg
* \>= 45.0 kg, \< 65.0 kg: 12.50 μg
* \>= 65.0 kg, \< 85.0 kg: 17.50 μg
* \>= 85.0 kg: 21.25 μg | 61 |
| 0.5 μg/kg Group The study drug was injected into the venous line of the dialysis circuit at the end of each dialysis session for 8 weeks (3 times weekly, 24 times in total). The injected volume of the study drug was determined based on the subject's dry weight on the day of dosing as below.
* \< 45.0 kg: 17.5 μg
* \>= 45.0 kg, \< 65.0 kg: 25.0 μg
* \>= 65.0 kg, \< 85.0 kg: 35.0 μg
* \>= 85.0 kg: 42.5 μg | 61 |
| 1.0 μg/kg Group The study drug will be injected into the venous line of the dialysis circuit at the end of each dialysis session for 8 weeks (3 times weekly, 24 times in total). The injected volume of the study drug was determined based on the subject's dry weight on the day of dosing as below.
* \< 45.0 kg: 35.0 μg
* \>= 45.0 kg, \< 65.0 kg: 50.0 μg
* \>= 65.0 kg, \< 85.0 kg: 70.0 μg
* \>= 85.0 kg: 85.0 μg | 61 |
| Placebo Group The study drug was injected into the venous line of the dialysis circuit at the end of each dialysis session for 8 weeks (3 times weekly, 24 times in total). | 63 |
| Total | 246 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 5 | 1 |
| Overall Study | Four consecutive missed doses of the study drug | 0 | 1 | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | 0.25 μg/kg Group | 0.5 μg/kg Group | 1.0 μg/kg Group | Placebo Group | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 36 Participants | 32 Participants | 33 Participants | 139 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 25 Participants | 29 Participants | 30 Participants | 107 Participants |
| Age, Continuous | 64.2 years STANDARD_DEVIATION 11.2 | 65.6 years STANDARD_DEVIATION 11.4 | 64.4 years STANDARD_DEVIATION 11.7 | 64.1 years STANDARD_DEVIATION 12.7 | 64.5 years STANDARD_DEVIATION 11.7 |
| Average NRS Score | 6.35 points STANDARD_DEVIATION 1.24 | 6.83 points STANDARD_DEVIATION 1.4 | 6.47 points STANDARD_DEVIATION 1.29 | 6.53 points STANDARD_DEVIATION 1.31 | 6.55 points STANDARD_DEVIATION 1.31 |
| Disease duration of Itch | 3.7 years STANDARD_DEVIATION 3.5 | 4.5 years STANDARD_DEVIATION 4.4 | 4.8 years STANDARD_DEVIATION 4.9 | 4.3 years STANDARD_DEVIATION 4.4 | 4.3 years STANDARD_DEVIATION 4.3 |
| Dry weight at the start of Sceening | 61.25 kg STANDARD_DEVIATION 13.86 | 59.98 kg STANDARD_DEVIATION 11.22 | 62.85 kg STANDARD_DEVIATION 13.39 | 60.63 kg STANDARD_DEVIATION 12.71 | 61.17 kg STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 61 Participants | 61 Participants | 63 Participants | 246 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hemodialysis History | 7.0 years STANDARD_DEVIATION 6.5 | 6.7 years STANDARD_DEVIATION 7.2 | 7.7 years STANDARD_DEVIATION 6.5 | 6.8 years STANDARD_DEVIATION 6.1 | 7.1 years STANDARD_DEVIATION 6.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 61 Participants | 61 Participants | 61 Participants | 63 Participants | 246 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 61 participants | 61 participants | 61 participants | 63 participants | 246 participants |
| Sex: Female, Male Female | 11 Participants | 16 Participants | 14 Participants | 20 Participants | 61 Participants |
| Sex: Female, Male Male | 50 Participants | 45 Participants | 47 Participants | 43 Participants | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 61 | 0 / 62 | 0 / 63 |
| other Total, other adverse events | 30 / 61 | 35 / 61 | 40 / 62 | 24 / 63 |
| serious Total, serious adverse events | 3 / 61 | 8 / 61 | 5 / 62 | 2 / 63 |
Outcome results
Primary
Change From Baseline in the Mean NRS Score at Week 8 of the Treatment Period
The primary analysis was performed using an MMRM with change from baseline in the mean NRS score at each time point as an objective variable; treatment group, time point, and treatment group-by-time point interaction as fixed effects; baseline mean NRS score and dynamic allocation factors, presence of prior treatment with nalfurafine hydrochloride, and presence of specific signs or symptoms to be confirmed in the screening period, as covariates; and subject as a random effect. Looking back on the period between the time of awakening on the previous day of assessment and the time of awakening on the day of assessment (including sleeping hours) once daily, subjects will assess the NRS score for the most severe itching by themselves. The most severe itching within the day will be assessed in integer on a scale ranging from 0 to 10, where 0 represents no itching and 10 represents worst itching imaginable.
Time frame: 8 weeks
Population: One subject of 1.0 μg/kg group was excluded from FAS due to deviation from one of the inclusion criteria. So, there is a discrepancy between the number of subjects in Participant flow and in Overall Number of Participants Analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25 μg/kg Group | Change From Baseline in the Mean NRS Score at Week 8 of the Treatment Period | -2.97 points | Standard Error 0.29 |
| 0.5 μg/kg Group | Change From Baseline in the Mean NRS Score at Week 8 of the Treatment Period | -3.65 points | Standard Error 0.3 |
| 1.0 μg/kg Group | Change From Baseline in the Mean NRS Score at Week 8 of the Treatment Period | -3.64 points | Standard Error 0.3 |
| Placebo Group | Change From Baseline in the Mean NRS Score at Week 8 of the Treatment Period | -2.86 points | Standard Error 0.29 |
p-value: 0.7795% CI: [-0.85, 0.63]MMRM
p-value: 0.03895% CI: [-1.55, -0.04]MMRM
p-value: 0.04195% CI: [-1.54, -0.03]MMRM