Proof-of-concept (PoC) Study of APD515

Study Overview
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Brief Summary
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A study to look at the effectiveness of a drug called APD515, designed to be applied to the lining inside the mouth, at relieving dryness of the mouth. Study will compare one week of treatment with APD515 to one week of treatment with matching placebo to see which has better effect on patient's mouth dryness, according to their own score.

Official Title
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Randomised, Double-blind, Placebo-controlled Phase II Proof-of-concept Study of APD515 Solution for Oromucosal and Oral Administration for Relief of Xerostomia in Patients With Cancer

Conditions
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Xerostomia in Advanced Cancer Patients

Intervention / Treatment
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* Drug: APD515
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years Able and willing to give written informed consent. 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. Subjective complaint of dry mouth, ongoing for at least two weeks prior to study entry. Capacity for salivary stimulation, as demonstrated by stimulated whole saliva flow rate > unstimulated whole saliva flow rate. Karnofsky performance score ≥ 60% or ECOG performance status ≤ 2. Adequate renal and hepatic function and hydration status: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 * upper limit normal (ULN); Serum urea < 1.5 * ULN and serum urea:creatinine ratio < 100 (where urea and creatinine expressed in the same units); Plasma sodium ≤ ULN. Adequate haematological function: Haemoglobin ≥ 9 g/dL; White blood count ≥ 1.0 * 10^9/L; Platelet count ≥ 50 *x 10^9/L. For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (e.g., abstinence from sexual intercourse, surgical sterilisation (of subject or partner) or a double-barrier method of contraception such as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in conjunction with partner's use of a condom) during the study and for a period of at least 48 hours afterwards. Exclusion Criteria: Confirmed diagnosis of Sjögren's syndrome. Prior radiotherapy for head & neck cancer, or other substantial doses of radiation delivered to the area of the mouth or salivary glands. Significant, symptomatic disease of the oral cavity, including oral candidosis or oral mucositis. Allergy to active ingredient or any of the excipients of APD515. Use of oral or topical (including ocular) pilocarpine or cevimeline in the two weeks prior to enrolment. Concomitant use of procainamide, quinidine or ganglionic blocking agents such as mecamylamine, pentolinium and trimethaphan. Intestinal or urinary obstruction. Myocardial infarction or intestinal anastomosis within the previous 6 months. Participation in an investigational drug or device study within 1 month prior to study entry. For female subjects only, a positive pregnancy test. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APD515<br>Active APD515 treatment 20 mg qds for 7 days | Drug: APD515<br>* 20 mg oromucosal-oral administration qds for 7 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* qds for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Xerostomia score | Change in score on 100 mm visual analogue scale | 1 week |