Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
120
Countries
1
Sites
1
Adult patients with a life-limiting condition or frailty who have the complaint dry mouth
This study intents to evaluate the effect of locally administered oral pilocarpine drops (3x 6 oral drops of pilocarpine per day ) in reducing complaints of dry mouth in a palliative population with xerostomia at the expense of limited adverse events, as compared to placebo.
Key facts
- Sponsor
- University Hospital Maastricht
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Not possible to specify
- Trial duration
- 5 Mar 2024 → 28 Apr 2025
- Decision date (initial)
- 2023-03-21
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2022-501084-41-00
- ClinicalTrials.gov
- NCT05506137
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Pharmacodynamic
This study intents to evaluate the effect of locally administered oral pilocarpine drops (3x 6 oral drops of pilocarpine per day ) in reducing complaints of dry mouth in a palliative population with xerostomia at the expense of limited adverse events, as compared to placebo.
Secondary objectives 12
- Dry mouth score in the pilocarpine group at all time-points compared to placebo
- Responders at week 8 and 12 among all patients who started with off-label, compassionate use of pilocarpine drops and who stopped the use of pilocarpine drops at week 4
- Severity of xerostomia in the pilocarpine group at all time-points, as compared to placebo
- The Global Perceived Effect (GPE) of the use of pilocarpine drops at t= 2, t= 4, t= 8 and t = 12, as compared to placebo
- Oral Health-Related quality of life (OHRQoL) measured with the Geriatric Oral Health Assessment Index (GOHAI-NL) upon pilocarpine treatment at all time-points, as compared to placebo
- Health-Related Quality of Life (HRQoL) measured with the EQ-5D-5L questionnaire upon pilocarpine treatment at t = 0, t = 4, t = 8, and t = 12, as compared to placebo
- Patient-Reported Functional Status (PRFS) upon pilocarpine treatment at all time-points, as compared to placebo
- The durability of the effect of the use of pilocarpine drops at week 8 and 12 on xerostomia
- Possible side effects related to the intake of pilocarpine medication, measured from week 2 (t = 2, t = 4, t = 8, t = 12 weeks)
- The adherence rate of patients, measured at t = 2, t = 4, t = 8, t = 12 weeks
- Patients’ views on applicability of pilocarpine to reduce complaints of dry mouth, measured at t = 4, t = 8, t = 12 weeks
- The cost-effectiveness of pilocarpine treatment, measured at t = 0, t = 4, t = 8, t = 12 weeks
Conditions and MedDRA coding
Adult patients with a life-limiting condition or frailty who have the complaint dry mouth
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- 18 years or older
- have a life-limiting condition or frailty
- have the complaint dry mouth ≥ 5 on an 11 point numerical rating scale (ranging from 0= no dry mouth to 10= worst dry mouth ever)
- fulfil the single SQ ‘Would I be surprised if my patient dies within the year? (no)
Exclusion criteria 3
- a life expectancy of less than 4 weeks (the primary endpoint at 4 weeks)
- have/had radiotherapy to the salivary glands or suffer from Sjögrens disease (impact on dry mouth)
- cognitively impaired to such an extent that there is insufficient understanding to complete questionnaires
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The main trial endpoint is the percentage responders at week 4 of topical pilocarpine administration (3x 6 oral drops of pilocarpine per day) for which a clinically relevant response is defined as at least a 2-point reduction on the 11-point NRS, as compared to baseline.
Secondary endpoints 12
- Mean difference in NRS dry mouth scores in the pilocarpine group at all time-points compared to placebo
- Percentage responders at week 8 and 12 among all patients who started with off-label, compassionate use of pilocarpine drops and who stopped the use of pilocarpine drops at week 4
- Mean difference in severity of xerostomia as measured with the xerostomia inventory scale (sXI) in the pilocarpine group at all time-points compared to placebo
- The Global Perceived Effect (GPE) of the use of pilocarpine drops at t= 2, t= 4, t= 8 and t = 12, when compared to the placebo group
- Change in Oral Health-Related quality of life (OHRQoL) measured with the Geriatric Oral Health Assessment Index (GOHAI-NL) upon pilocarpine treatment at all time-points, when compared to the placebo group
- Change in Health-Related Quality of Life (HRQoL) measured with the EQ-5D-5L questionnaire upon pilocarpine treatment at t = 0, t = 4, t = 8, and t = 12, when compared to the placebo group
- Change in Patient-Reported Functional Status (PRFS) upon pilocarpine treatment at all time-points
- The durability of the effect of the use of pilocarpine drops at week 8 and 12 on xerostomia
- Possible side effects related to the intake of pilocarpine medication, measured from week 2 (t = 2, t = 4, t = 8, t = 12 weeks)
- The adherence rate of patients, measured at t = 2, t = 4, t = 8, t = 12 weeks
- Patients’ views on applicability of pilocarpine to reduce complaints of dry mouth, measured at t = 4, t = 8, t = 12 weeks
- The cost-effectiveness of pilocarpine treatment, measured at t = 0, t = 4, t = 8, t = 12 weeks
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB14870MIG · Substance
- Active substance
- Pilocarpine Hydrochloride
- Pharmaceutical form
- SOLUTION
- Route of administration
- ORAL USE
- Max daily dose
- 10.8 mg milligram(s)
- Max total dose
- 10.8 mg milligram(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Instead of eye drops, oral drops are made
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
University Hospital Maastricht
- Sponsor organisation
- University Hospital Maastricht
- Address
- P. O. Box 616
- City
- Maastricht
- Postcode
- 6200 MD
- Country
- Netherlands
Scientific contact point
- Organisation
- University Hospital Maastricht
- Contact name
- Prof. dr. MHJ van den Beuken - van Everdingen
Public contact point
- Organisation
- University Hospital Maastricht
- Contact name
- Prof. dr. MHJ van den Beuken - van Everdingen
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 120 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Maastricht University
EPZ MUMC+, P Debyelaan 25, 6229 HX, Maastricht
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2023-04-11 | 2023-06-06 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-9544
- Halt date
- 2023-12-08
- Member states concerned
- Netherlands
- Publication date
- 2023-12-11
- Reason
- Medicinal Product related
- Explanation
- After the blinded four week active study period, where patients receive pilocarpine or placebo as IMP, every participant is offered an eight week unblinded extension treatment period with off-label pilocarpine eye drops (Minims). The off-label pilocarpine was not delivered as IMP but as regular medication via the patients' pharmacy. This is reported as serious breach.
- Follow-up measures
- Actions taken
As soon as we became aware, the METC and the Grant Supplier (ZonMw) were informed (December 4 2023). The METC discussed the issue December 6, we received an answer December 8 2023. Based on the answer of the METC the inclusion was set on hold December 6.
Planned actions
A substantial amendment will be submitted: Study stop after 4 weeks (this is the primary outcome measure) instead of 12 weeks; (secondary) measurements at 8 and 12 weeks will no longer be assessed.
Patients who want to make use of off-label pilocarpine treatment after 4 weeks will be advised to contact their general practitioner. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Corrective measures 1 · Art. 77 CTR
Corrective measure CM-NL-0001
- Member state
- Netherlands
- Publication date
- 2023-12-21
- Type
- 3
- Reason
- 2
- Immediate action required
- Yes
- Justification
- • Incorrect prescribing as the reason for the serious breach must be taken into account in the CTIS notification (in a update on this Serious Breach)
Toelichting:
Gaarne de melding in CTIS aanpassen door de onderzoeker. De oorzaak van de serious breach was het foutief (afwijkend t.o.v. het studieprotocol) regulier voorschrijven (pilocarpine medicatie op recept onherkenbaar als onderdeel van een studie) i.p.v. het voorschrijven van het open label IMP en het trialrecept in te leveren bij de clinical trial unit. Deelnemers werden tevens door de studiearts foutief verwezen naar een reguliere apotheek i.p.v. de clinical trial unit van het ziekenhuis.
• Request advice from one or more committee DB members
• The committee requests an approval of the Substantial Modification with removal of the extension phase before the study can start again.
Graag verwijs ik u ook nog naar de separate email correspondentie d.d. 13-12-2023 waarin gevraagd is deelnemers die nu nog in het onderzoek zitten te informeren over het feit dat zij niet kunnen doorstromen/participeren in deel II (optionele fase) van het onderzoek (week 5 t/m 12).
• Participants currently on IMP treatment need to be informed that the extension phase will be canceled and an impact-analysis should be written, in which the consequences for participant’s insurance, absence of drug accountability, inappropriate labeling, and the risks of a different dosage form (multidose dropper bottles versus single-use minims) must be discussed.
Aanvullend:
De commissie wil u graag attenderen op de regelgeving van regulier off-label voorschrijven, waarbij de basis is dat iets verdisconteerd dient te zijn in een richtlijn en waarvan de meerwaarde reeds is aangetoond t.o.v. een geregistreerd alternatief.
Off-label voorschrijven | Standpunt | Inspectie Gezondheidszorg en Jeugd (igj.nl)
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| SUMMARY OF THE RESULTS OF THE CLINICAL TRIAL Pilocarpine SUM-128073
|
2026-04-09T09:14:17 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Lekensamenvatting onderzoek Pilocarpinedruppels bij droge mond | 2026-04-09T09:14:28 | Submitted | Laypersons Summary of Results |
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Lekensamenvatting onderzoek Pilocarpinedruppels bij droge mond | 1 |
| Protocol (for publication) | D1_Protocol 2022-501084-41-00 redacted | 4 |
| Protocol (for publication) | D4_CRF Droge Mond studie | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Pilocarpine | 1 |
| Summary of results (for publication) | SUMMARY OF THE RESULTS OF THE CLINICAL TRIAL Pilocarpine | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NL 2022-501084-41-00. | 2 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-11-18 | Netherlands | Acceptable 2023-03-20
|
2023-03-21 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-06-16 | Netherlands | Acceptable | 2023-08-21 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2023-12-22 | Netherlands | Acceptable 2024-03-04
|
2024-03-04 |
| 4 | SUBSTANTIAL MODIFICATION | SM-5 | 2024-06-20 | Netherlands | Acceptable 2024-07-11
|
2024-07-11 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2024-07-12 | |||
| 6 | SUBSTANTIAL MODIFICATION | SM-6 | 2024-08-09 | Netherlands | Acceptable 2024-08-27
|
2024-08-27 |