Study of Itch Control by VLY-686 in Healthy Volunteers After Intradermal Injections of Substance P

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Vanda Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01919944
First received: August 2, 2013
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to test whether VLY-686 can prevent or reduce the itch and dermatological reaction observed after healthy volunteers are injected with Substance P in comparison with placebo.


Condition Intervention Phase
Pruritus
Drug: VLY-686
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Four-Way Crossover Study on Itch Control by VLY-686 Administration in Healthy Volunteers After Intradermal Injections of Substance P

Resource links provided by NLM:


Further study details as provided by Vanda Pharmaceuticals:

Primary Outcome Measures:
  • Itch severity score on the Verbal Rating Scale [ Time Frame: 20 minutes after Substance P injection ] [ Designated as safety issue: No ]
  • Itch severity score on the Visual Analog Scale [ Time Frame: 20 minutes after Substance P injection ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dose response of VLY-686 and reduction of itch severity [ Time Frame: 20 minutes after substance P injection ] [ Designated as safety issue: No ]
  • Number of adverse events in subjects taking VLY-686 [ Time Frame: 24 hours after Substance P injection ] [ Designated as safety issue: Yes ]
  • Size of injection site erythema [ Time Frame: 1-20 minutes after Substance P injection ] [ Designated as safety issue: No ]
  • Number of adverse events in subjects taking placebo [ Time Frame: 20 minutes after Substance P inection ] [ Designated as safety issue: Yes ]
  • Size of injection site and urticaria [ Time Frame: 20 minutes after Substance P injection ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: August 2013
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VLY-686 20 mg
Single dose, 20 mg VLY-686, administered as two 10 mg VLY-686 oral capsules
Drug: VLY-686
capsules containing either 10 mg or 50 mg VLY-686
Experimental: VLY-686 50 mg
Single dose, 50 mg VLY-686, administered as one 50 mg VLY-686 oral capsule and one placebo capsule mimicking the VLY-686 50 mg capsule
Drug: VLY-686
capsules containing either 10 mg or 50 mg VLY-686
Drug: Placebo
Sugar capsule to mimic either VLY-686 10 mg capsule or 50 mg capsule
Experimental: VLY-686 100 mg
Single dose, 100 mg VLY-686, administered as two 50 mg VLY-686 oral capsules
Drug: VLY-686
capsules containing either 10 mg or 50 mg VLY-686
Placebo Comparator: Placebo
Single dose, placebo, administered as either two 10 mg oral capsules or two 50 mg oral capsules
Drug: Placebo
Sugar capsule to mimic either VLY-686 10 mg capsule or 50 mg capsule

Detailed Description:

This is a double-blind, randomized, 4-way crossover, pharmacokinetic and pharmacodynamic (PK/PD) study to compare the cutaneous vasoreactive intensity to intradermal injections of Substance P in healthy volunteers receiving oral doses of 20 mg, 50 mg or 100 mg VLY-686 or a matching placebo. Twelve healthy male subjects satisfying the selection criteria for the study will be enrolled. Each subject will participate in a screening period (up to 21 days prior to dosing), four one-day treatment periods each separated by a 7 (±2 days) day washout period, and an end-of-study evaluation prior to discharge from the study. This protocol also includes an option of subjects administered daily doses of study medication between Periods 3 and 4. The treatment periods will be in a randomized sequence consisting of 1) 20 mg VLY-686, 2) 50 mg VLY-686, 100 mg VLY-686 and 4) placebo. In each of the study periods, Substance P will be injected 5 times: pre-dose (the night before), 2, 4, 8 and 12 hours (± 10 minutes) after study medication administration. A dose of 100 μL of a 2.5 nmol/mL sterile solution of Substance P will be injected each time. Overall, subjects will be administered 1.25 nmol of Substance P in around 24 hours (5 doses). Substance P injections will be given in the volar of the forearm, alternating right and left and avoiding injections in an area adjacent to the area previously injected. The subject's forearm will be covered during and after each injection to avoid potential biases in the scoring of the Verbal Rating Scale (VRS) and Visual Analog Scale (VAS). Additionally, blood samples for VLY-686 pharmacokinetic (PK) analysis will be collected each period at pre-dose, 1, 3, 6, 10, and 24 hours after study medication administration.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males 18 - 45 years of age, inclusive;
  • Non-smokers, per medical history, or ex-smokers for a period of ≥1 year;
  • Subjects with Body Mass Index (BMI) of ≥18.5 and ≤30 kg/m2 (BMI = weight (kg)/ [height (m)]2);
  • Vital signs (in sitting position after 3 minutes of rest) which are within the ranges shown below (inclusive):
  • Body temperature between 35.4-37.8 °C;
  • Systolic blood pressure between 91-130 mmHg;
  • Diastolic blood pressure between 51-90 mmHg;
  • Pulse rate between 50-100 bpm;
  • Respiratory rate between 10-20 breaths per minute;
  • Ability and acceptance to provide written informed consent;
  • Willing and able to comply with study requirements and restrictions;
  • Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis.

Exclusion Criteria:

  • Past or present history of atopy (atopic dermatitis problems, urticaria, asthma or allergic rhinitis) with no ascertained intolerance to histamine;
  • Past or present skin disease;
  • Lesions or any skin changes in the forearms in the month prior to the Screening Visit;
  • History of neurological diseases;
  • Past or present pain-related diseases such as cluster headaches, migraine, or back pain;
  • Treatment with all topical cream and ointments including cosmetics applied on the forearm in the 10 days prior to the screening visit;
  • Participation in the evaluation of any investigational product for 3 months before this study, calculated from the first day of the month following the last visit of the previous study;
  • Exposure (within 2 weeks of the Baseline Visit) to any prescription medication or over-the-counter medication including dietary supplements and/or herbal remedies, except those listed on Section 8.2;
  • Exposure (within 4 weeks of the Screening Visit) to any antihistamines, anxiolytics, antidepressants, pain killers including triptanes, neuroleptics, or sleep medications;
  • Treatment with any medication known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening Visit;
  • Administration of medications containing corticosteroids or adrenocorticotropic hormone in the three months prior to the Screening Visit;
  • Electrocardiogram reading considered outside the normal limits by the investigator (e.g. abnormally prolonged QTc corrected by Fridericia's method > 450 msec in males, on ECG tracing). The following conduction abnormalities may confound QTc analysis and should be avoided if possible: PR > 220 msec, 2nd or 3rd degree AV block, intraventricular conduction delay with QRS > 120 msec, left branch bundle block, right branch bundle block or Wolff-Parkinson-White syndrome;
  • Blood donation in the last 3 months or donation of at least 1500 mL blood (including this study) within the last year;
  • History of liver disease and/or positive for one or more of the following serological results:
  • A positive hepatitis C antibody test (anti-HCV);
  • A positive hepatitis B surface antigen (HBsAg);
  • A positive HIV test result ;
  • Not willing to sign the informed consent or not able to understand completely the study objectives or risks;
  • Clinically relevant abnormalities in clinical lab or physical assessments performed at the screening visit;
  • Lack of sensitivity to Substance P and histamine or sensitivity to saline at the Screening Visit;
  • Any other sound medical reason as determined by the clinical Investigator.
  • Drug, alcohol, caffeine, tobacco: history of drug, alcohol (>2 drinks/day for males, defined according to USDA Dietary Guidelines 2010), caffeine (>5 cups coffee/tea/day), smokers;
  • Diet: abnormal diets (<1600 or >3500 calories/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01919944

Locations
Switzerland
Vanda Investigational Site
Arzo, Switzerland, CH 6864
Sponsors and Collaborators
Vanda Pharmaceuticals
Investigators
Principal Investigator: Milko Radicioni, MD Cross Research SA
  More Information

No publications provided

Responsible Party: Vanda Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01919944     History of Changes
Other Study ID Numbers: VP-VLY-686-1101
Study First Received: August 2, 2013
Last Updated: December 5, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by Vanda Pharmaceuticals:
itch

Additional relevant MeSH terms:
Pruritus
Skin Diseases
Skin Manifestations
Signs and Symptoms
Substance P
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014