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Open-label, Single-arm Study of NT 201 in Patients With Chronic Sialorrhea

Open-label, Single-arm Study of NT 201 in Patients With Chronic Sialorrhea

95

The full analysis set (FAS) consisted of 57 subjects in Group A and 34 subjects in Group B. The proportion of males was 75.4% (43/57 subjects) in Group A and 76.5% (26/34 subjects) in Group B. The mean age (SD) was 67.6 (9.7) years in Group A and 67.5 (14.2) years in Group B. Mean body weight (SD) was 58.5 (11.9) kg in Group A. In Group A, the proportion of diseases probable caused chronic sialorrhea (overlap tabulation) was 87.7% (50/57 subjects) for Parkinson's disease, 7.0% (4/57 subjects) for atypical parkinsonism, 5.3% (3/57 subjects) for post-stroke, and 1.8% (1/57 subjects) for other [symptomatic epilepsy and aphasia (identical to post-stroke subjects)], and no subjects after traumatic brain injury. In Group B, 73.5% (25/34 patients) had Parkinson's disease, 8.8% (3/34 patients) had muscular dystrophy, ALS (amyotrophic lateral sclerosis) and others (congenital myopathy, multiple sclerosis) in 5.9% (2/34 patients) each, and atypical parkinsonism and cerebral palsy in 2.9% (1/34 patients) each. The mean of baseline uSFR (Unstimulated Salivary Flow Rate) (SD) was 0.21 (0.19) g/min in Group A. The mean in the sum score of baseline DSFS (Drooling severity and frequency scale) (SD) was 7.51 (0.89) in Group A and 7.62 (1.02) in Group B. There were 3 subjects in Group A and 2 in Group B had the history of treatment with botulinum toxin (botulinum toxin A).

Number of subjects enrolled: 95 (Group A:61 subjects, Group B:34 subjects) Safety analysis set: 92 subjects (Group A:58 subjects, Group B:34 subjects) Full analysis set (FAS): 91 subjects (Group A:57 subjects, Group B:34 subjects)

The incidence of adverse events was 82.6% (76/92 subjects) and that of adverse drug reactions was 21.7% (20/92 subjects) in the overall study. Adverse events leading to death occurred in 3 subjects, all events were concluded unrelated to Investigational Product. The incidence of serious adverse events was 22.8% (21/92 subjects), and the incidence of serious adverse drug reactions was 3.3% (3/92 subjects). The incidence of adverse events leading to the discontinuation was 9.8% (9/92 subjects), and the incidence of adverse events of high severity was 8.7% (8/92 subjects). There was no trend that the increasing number of administrations leads to make the incidence of adverse events higher. The most common adverse event in the overall study was COVID-19[14.1%(13/92 subjects)], followed by contusion [13.0% (12/92 subjetcs)], pyrexia [9.8% (9/92 subjects)], and dry mouth and dysphagia [8.7% (8/92 subjects)]. The adverse event with a notable difference between the incidence in Group A and Group B was pneumonia aspiration [Group A:0.0% (0/58 subjects), Group B:14.7% (5/34 subjects)]. There was no trend that the increasing number of administrations leads to make the incidence of adverse events higher. Adverse drug reactions occurred in 2 or more subjects were dry mouth, dysphagia [8.7% (8/92 subjects), and thirst [3.3% (3 /92 subjects)] in the overall study. The incidence of dry mouth and dysphagia in Group B was higher than Group A. There was no trend that the increasing number of administrations leads to make the incidence of adverse drug reactions higher.

<Primary endpoint> As the change from baseline (g/min) in uSFR at 4 weeks after the first administration, the least squares mean (MMRM analysis) (SEM) was -0.08 (0.009) (95% confidence interval: -0.10, -0.06) and the prespecified efficacy criteria (the upper limit of the 95% confidence interval of the change in uSFR at 4 weeks after the first administration was below the thresholds of -0.04 g/min). The primary endpoint was achieved. <Secondary endpoints> - At all points, uSFR showed a similar reduction. - Subject's GICS (responded by caregivers if the subjects were unable to) showed improved trend in the combined group and in each group. - The sum and sub scores (severity score, frequency score) of DSFS decreased (improved) in the combined group and in each group. - mROMP drooling score also decreased (improved). The same therapeutic effect as the single administration was observed after each administration.

NT 201 100U was administered three times to patients with chronic sialorrhea.The dosing intervals were 16 weeks (range: 14-18 weeks), and the total observation period was 48 weeks (range: 56-72 weeks). Administration of NT 201 100 U reduced uSFR and improvement in sialorrhea symptoms. Regarding safety, dysphagia and dry mouth were relatively common, but no new safety concerns were identified.

Nov. 14, 2025

Aug. 07, 2025

https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mdc3.70259

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2051210082

Fujita Mariko

Teijin Pharma Limited

2-1, Kasumigaseki 3-chome, Chiyoda-ku, Tokyo 100-8585, Japan

clintrials@teijin.co.jp

Fujita Mariko

Teijin Pharma Limited

2-1, Kasumigaseki 3-chome, Chiyoda-ku, Tokyo 100-8585, Japan

+81-3-3506-4602

clintrials@teijin.co.jp

Complete

Oct. 01, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

(1) Patients for whom written informed consent has been obtained from the patient or the legally acceptable representative before participating in the clinical trial.
(2) Men and women aged >=20 and <=80 years at the time of informed consent
(3) Patients who meet all of the following 1) to 3) at the pre-enrollment examination
1) Drooling severity and frequency scale (DSFS) with a total score of 6 or more.
2) DSFS scores of 2 or more for each item (severity and frequency)
3) Modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) Drooling A) score of 3 or more
(4) Patients continuously meeting the inclusion criteria (3) from 12 weeks or more before the day of pre-enrollment examination.
(5) Patients who have any disease presumed as a causes of sialorrhea [e.g., Parkinson's disease, atypical parkinsonism, stroke, traumatic brain injury, cerebral palsy, amyotrophic lateral sclerosis (ALS), muscular dystrophy, etc.]

[Group A]:
Patients who meet both 1) and 2) below
1) Patients who have been diagnosed with any of the following diseases i) to iv) and have had the disease for at least 24 weeks since the onset of the disease by the day of the pre-enrollment examination.
i) Isolated Parkinson's disease or hereditary Parkinson's disease diagnosed according to criteria of UK Parkinson's Disease Brain Bank (UKPDSBB)
ii) Clinically diagnosed atypical parkinsonism following a) to c)
a) Multiple system atrophy
b) Progressive supranuclear palsy
c) Corticobasal degeneration
iii) Stroke
iv) Traumatic brain injury
2) Individuals who are able to comply with the schedules of observation and examination specified in Group A, including uSFR measurements

[Group B]:
Patients not applicable to [Group A]. However, after the sponsor has completed enrollment in Group A, patients who fall into Group A can also be enrolled in Group B.

(1) Patients with a score of 3 or more on mROMP Swallowing symptoms A) or a score of 4 or more on the C) regarding swallowing function at the pre-enrollment examination. However, patients who use a tube feeding is used for nutritional support do not fall under mROMP Swallowing symptoms C) 5 "I had to use a feeding tube".
(2) Patients who have experienced aspiration pneumonitis twice or more, patients who had the experience once and are judged by the investigator to be at increased risk of the recurrence, or patients who have not had gastrostomy after TPPV induction.
(3) Patients with generalized neuromuscular junction disorders (such as myasthenia gravis and Lambert-Eaton syndrome)
(4) Patients with a history (or complication) of infection or tumor in the salivary glands or at the intended injection site. However, infections in childhood such as parotitis are permissible.
(5) Patients who are judged by the investigator to be at risk of preventing a safe participation in the clinical trial due to extremely poor dental oral health status.
(6) Patients who have received other investigational or unapproved drugs within 14 weeks prior to the date of the pre-registration examination.
(7) Patients who have undergone functional neurosurgery (deep brain stimulation, stereotactic disruption) or focused ultrasound within 24 weeks prior to the date of the pre-registration examination
(8) Patients who have previously undergone head and neck surgery or radiotherapy (e.g., salivary gland surgery or salivary gland radiotherapy) for the treatment of sialorrhea.
(9) Patients who are receiving muscle relaxants/drugs with muscle relaxant effects and anticoagulants. However, aspirin and antiplatelet agents are permissible.
(10) Patients who need to use (implementation) a prohibited concomitant medication or change in dosage and administration of a restricted concomitant medication after the date of the pre-registration examination

[Exclusion Criteria Applied Only to Group A].
(11) Patients who are unable to place the saliva collection swabs in their mouth and keep resting for 5 minutes
(12) Patients who are unable to open their mouth spontaneously
(13) Patients with Alzheimer's disease or other dementias who are judged by the investigator to have an impact on the evaluation of the study.

[Exclusion Criteria Applied to Group B Only].
(14) [Exclusion criteria only applicable to patients with ALS].
Patients who have a progressive decline in respiratory function and may receive noninvasive positive pressure ventilation (NPPV) or tracheostomy-guided positive pressure ventilation (TPPV) in 1 yr. However, those who have already undergone TPPV are not eligible for this exclusion criterion.
(15) [Exclusion criteria only applicable to patients with ALS].
Patients whose percent forced vital capacity (%FVC) is <80% at the pre-enrollment examination. However, those who have already undergone TPPV are not eligible for this exclusion criterion.

Both

chronic sialorrhea

NT 201(100U) is administered intraglandally once every 16 weeks for a total three times.

Change in Unstimulated Salivary Flow Rate (uSFR) from pre-first study treatment (baseline) to 4 weeks post-treatment in Group A

+81-561-62-3311

Sept. 08, 2021

none