VA106483 Dose Response in Females

An Open Label, Dose Escalation Study to Assess Intra-Subject Dose Response to VA106483 in Female Subjects

The purpose of this study is to describe the pharmacokinetics and pharmacodynamics of VA106483 in female subjects.

Study Overview

• Status: Completed
• Conditions: Nocturia
• Intervention / Treatment: Drug: VA106483; Other: Placebo

Detailed Description

Nocturia, defined as waking to void at least once per night between periods of sleep, is a common complaint and shows an age-dependent increase in both prevalence and severity (number of nocturnal voids). The most common causes are detrusor over-activity, reduced nighttime functional bladder capacity, and nocturnal polyuria.

VA106483 is a selective vasopressin V2-receptor agonist in development for nocturia. VA106483 is a non-peptide drug that displays much improved oral availability over desmopressin and low dependence on glomerular filtration for its elimination.

VA106483 has been administered to 184 subjects (including healthy adult subjects [males and females], children [males and females] with nocturia and 48 elderly males [aged 65 years and over]). It has been administered as single doses both intravenously, up to doses of approximately 250 mg and orally up to 50 mg It is also being investigated in approximately 123 male subjects (two-thirds on active medication, one third on placebo) with nocturia in a current study with dosing for up to 8 weeks.

This intra-subject dose escalation study has previously been conducted in 10 elderly male subjects to determine whether subjects demonstrated a dose-dependent pharmacokinetic and pharmacodynamic (urine osmolality and diuresis) response and whether the dose of VA106483 could be titrated within an individual patient to achieve optimal clinical response in clinical practice. Given that to date, only 8 females have been exposed to VA106483, the purpose of this study is to confirm that the described duration of pharmacokinetics and pharmacodynamics of VA106483 in males is similar in females.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Quintiles Phase I Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female subjects 40 years and above
• BMI 18 to 32 kg/m2
• Using adequate contraception and providing negative pregnancy tests pre-dose
• In good health as determined by medical history and screening tests
• Subject is willing and able to abstain from alcohol and caffeine-containing food and beverages 72 hours prior to dosing and throughout the study
• Provide written, informed consent

Exclusion Criteria:

• Pregnancy or lactation
• Evidence of serious pathology or diseases including heart, hormone, liver and kidney, psychiatric and neurological problems, including syndrome of inappropriate antidiuretic hormone secretion, polydipsia or diabetes insipidus
• Likely to be hypersensitive to VA106483
• History of any relevant allergy
• Participation in a clinical study within 30 days
• Donation of blood (500 mL) within 60 days prior to dosing
• A history of alcohol abuse or drug addiction
• Positive results for HIV, HBV or HCV or drugs of abuse
• Currently taking any diuretics or clinically significant cytochrome 3A4 inhibitors or inducers
• Use of any non-prescription preparation within 72 hours prior to dosing, with the exception of ibuprofen, and acetaminophen used at recommended doses
• Treatment within the previous 3 months of drugs known to have a well defined potential for hepatoxicity
• Current smokers or recent ex-smokers
• Other protocol defined eligibility criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar pill	Other: Placebo; Placebo on Day 1
Experimental: VA106483 1mg	Drug: VA106483; 1 mg VA106483 on Day 3, 2 mg VA106483 on Day 5 and 4 mg VA106483 on Day 7
Experimental: VA106483 2mg	Drug: VA106483; 1 mg VA106483 on Day 3, 2 mg VA106483 on Day 5 and 4 mg VA106483 on Day 7
Experimental: VA106483 4mg	Drug: VA106483; 1 mg VA106483 on Day 3, 2 mg VA106483 on Day 5 and 4 mg VA106483 on Day 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	VA106483 plasma concentration pre-dose over a 24hr post-dose period to assess pharmacokinetics of each dose level	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics	Urine volume and osmolality	10 days
Safety and Tolerability	AEs, laboratory safety tests, vital signs and ECG, physical examination.	10 days

Collaborators and Investigators

• Sponsor: Vantia Ltd
• Investigators: Principal Investigator: Ralph Schutz, Quintiles Phase I Services

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: July 19, 2010
• First Submitted That Met QC Criteria: July 27, 2010
• First Posted (Estimate): July 28, 2010

Study Record Updates

• Last Update Posted (Estimate): December 1, 2010
• Last Update Submitted That Met QC Criteria: November 30, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Nocturia; Water-loading; Females
• Additional Relevant MeSH Terms: Lower Urinary Tract Symptoms; Urological Manifestations; Nocturia
• Other Study ID Numbers: 483-007