E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048223 |
E.1.2 | Term | Xerostomia |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To test the effectiveness of APD515 at relieving dry mouth in advanced cancer patients. |
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E.2.2 | Secondary objectives of the trial |
To confirm the safety and tolerability of APD515.
To assess patient preference for APD515. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged ≥ 18 years
2. Able and willing to give written informed consent.
3. Confirmed primary neoplasm at any site (apart from non-melanoma skin cancers), for which first-line cytotoxic therapy has been completed more than one month prior to study entry. Ongoing palliative, hormonal, cytostatic or “targeted” (e.g., monoclonal antibody, tyrosine kinase inhibitor, etc) therapy is permitted, provided that the risk of oral mucositis in the subject is not judged to be significant.
4. Subjective complaint of dry mouth, ongoing for at least two weeks prior to study entry.
5. Capacity for salivary stimulation, as demonstrated by stimulated whole saliva flow rate > unstimulated whole saliva flow rate.
6. Karnofsky performance score ≥ 60% or ECOG performance status ≤ 2.
7. Adequate renal and hepatic function and hydration status:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 x upper limit normal (ULN);
• Serum urea < 1.5 x ULN and serum urea:creatinine ratio < 100 (where urea and creatinine expressed in the same units);
• Plasma sodium ≤ ULN.
8. Adequate haematological function:
• Haemoglobin ≥ 9 g/dL;
• White blood count ≥ 1.0 x 10^9/L;
• Platelet count ≥ 50 x 10^9/L.
9. Willing to use an effective form of contraception during the study and for a period of fourteen days afterwards:
• For male subjects adequate contraception may be achieved through abstinence from sexual intercourse or use of a double barrier method of contraception.
• For female subjects adequate contraception may be achieved through abstinence from sexual intercourse, surgical sterilization (of subject or partner), by being post-menopausal (no spontaneous menstrual period for at least one year), or by the use of a double barrier method of contraception. |
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E.4 | Principal exclusion criteria |
1. Confirmed diagnosis of Sjögren’s syndrome.
2. Prior radiotherapy for head & neck cancer, or other substantial doses of radiation delivered to the area of the mouth or salivary glands.
3. Significant, symptomatic disease of the oral cavity, including oral candidosis or oral mucositis.
4. Allergy to active ingredient or any of the excipients of APD515.
5. Use of oral or topical (including ocular) pilocarpine or cevimeline in the two weeks prior to enrolment.
6. Concomitant use of procainamide, quinidine or ganglionic blocking agents such as mecamylamine, pentolinium and trimethaphan.
7. Intestinal or urinary obstruction.
8. Myocardial infarction or intestinal anastomosis within the previous 6 months.
9. Participation in an investigational drug or device study within 1 month prior to study entry.
10. For female subjects only, a positive pregnancy test.
11. Female subjects who are lactating.
12. Any condition or disease detected during the medical interview/physical examination that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the Investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is the score on a 100mm visual analogue scale (VAS) in response to the question “How dry is your mouth at present?” |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
No interim analysis is planned. Anaylsis is planned after LPLV and database lock. |
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E.5.2 | Secondary end point(s) |
To characterise further the efficacy profile of APD515 in adult cancer patients with xerostomia.
To assess the safety of APD515 compared to placebo in adult cancer patients with xerostomia.
|
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
No interim analysis is planned. Anaylsis is planned after LPLV and database lock. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |