Proof-of-concept (PoC) Study of APD515

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

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.

Study Overview

• Status: Completed
• Conditions: Xerostomia in Advanced Cancer Patients
• Intervention / Treatment: Drug: APD515; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • University of Copenhagen
  • Hillerød, Denmark
    • Hillerød Hospital
  • Århus, Denmark
    • Århus University Hospital
• United Kingdom
  • Cheltenham, United Kingdom
    • Sue Ryder Leckhampton Court Hospice
  • Coventry, United Kingdom
    • Coventry and Warwickshire Partnership Trust
  • Guildford, United Kingdom
    • Royal Surrey County Hospital
  • Mansfield, United Kingdom
    • John Eastwood Hospice
  • Norwich, United Kingdom
    • Priscilla Bacon Lodge
  • Nottingham, United Kingdom
    • City Hospital Hayward House Specialist Palliative Care Unit
  • Scarborough, United Kingdom
    • Scarborough General Hospital
  • Shrewsbury, United Kingdom
    • Severn Hospice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Acacia Pharma Ltd

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 7, 2011
• First Submitted That Met QC Criteria: April 7, 2011
• First Posted (Estimate): April 8, 2011

Study Record Updates

• Last Update Posted (Estimate): May 16, 2013
• Last Update Submitted That Met QC Criteria: May 15, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Xerostomia
• Other Study ID Numbers: DX10008