Implant Pharmacokinetic and Pharmacodynamic Study

A Phase Ib Study to Confirm the Pharmacokinetics and Melanogenic Potential of Controlled-Release Bioresorbable Implants of Afamelanotide in Healthy Volunteers

This is a single center, pharmacokinetic and pharmacodynamic study in healthy volunteers. Twenty four subjects will be enrolled in the study and will be assigned to receive either a 16 mg afamelanotide bioresorbable implant from the current manufacturing process or a 16 mg afamelanotide bioresorbable implant from the optimized manufacturing process. Implants will be administered subcutaneously.

The following procedures will be conducted throughout the study:

• Collection of blood samples for analysis of afamelanotide concentrations
• Measurement of skin reflectance for estimation of melanin density, and luminance (L*), blue/yellow colour hue (b*)
• Safety monitoring

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Afamelanotide Group 1; Drug: Afamelanotide Group 2

Detailed Description

The objective of the proposed study is to confirm that the pharmacokinetic and pharmacodynamic properties of implants eluting 16 mg of afamelanotide produced by this final optimized manufacturing process are essentially the same as those of implants manufactured with the same formulation that have been used in earlier clinical studies

The study will involve the use of an implant, which comes in the form of a small rod to be administered under the skin.

For this study, afamelanotide has been formulated as a controlled release depot injection (implant). This means that the afamelanotide will be released slowly into the body over a few days. Once inserted, the implant will remain in the body after afamelanotide has been released and will slowly dissolve.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Caucasian adults aged between 18 and 45 years (inclusive).
• Free of significant abnormal findings as determined during the screening procedure by surgical and medical history, physical examination, ECG, clinical laboratory testing and vital signs.
• BMI between 18 and 30 kg/m2 (inclusive).
• No history of drug abuse, licit or illicit (including alcohol).
• Agree not to use any medications (prescribed medicines, over-the-counter medications, dietary supplements or nutraceuticals) without pre-approval by the Principal Investigator or nominee during the 7 days preceding the study, and during the course of the study (until Day 60)
• Willing to take precautions to prevent pregnancy until completion of the study (Day 60).
• Able to understand and sign the written Informed Consent Form.
• Able and willing to follow the Protocol requirements, including refraining from the use of melanogenic (tanning) products and recreational sun or UV light exposure from the start of the study until Day 60

Exclusion Criteria:

• Any significant history of allergy and/or sensitivity to any of the contents of study drug product.
• Any significant history of allergy and/or sensitivity to lignocaine or other local anaesthetic.
• Any evidence of organ dysfunction or any clinically significant deviation from normal in the physical or clinical determinations.
• Personal history of melanoma, dysplastic nevus syndrome or family history of melanoma in a first degree relative.
• Any evidence at the screening medical examination of hypertension or hypotension. Hypertension is defined as three separate readings that persistently read over 140/90 mmHg systolic/diastolic. Hypotension is defined as three separate readings that persistently read under 90/50 mmHg systolic/diastolic.
• A pulse rate of less than 50 beats/minute.
• Any significant illness during the 4 weeks before the study screening period.
• Any contraindication to blood sampling.
• Any factor that may interfere with the skin reflectance measurements (e.g. vitiligo, albinism, excessive number of moles, or excessively hairy skin).
• Positive screening urine drugs of abuse test.
• Participation in any clinical study during the 4 weeks before the study screening period.
• Has donated 400 mL or more of blood or had significant blood loss during the 8 weeks preceding screening.
• Has donated plasma within the 7 days preceding screening.
• Have consumed alcohol during the 24 hours prior to Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afamelanotide Group 1; A 16 mg bioresorbable afamelanotide implant (Group 1) from the previous manufacturing process.	Drug: Afamelanotide Group 1; One 16 mg bioresorbable afamelanotide implant (Group 1) from the previous manufacturing process.; Other Names: afamelanotide
Experimental: Afamelanotide Group 2; A 16 mg bioresorbable afamelanotide implant (Group 2) from the optimized final manufacturing process.	Drug: Afamelanotide Group 2; One 16 mg bioresorbable afamelanotide implant (Group 2) from the optimized final manufacturing process.; Other Names: afamelanotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in skin melanin density	To confirm serial changes in skin melanin density by reflectance spectrophotometry following administration of the final formulation afamelanotide bioresorbable implants in healthy volunteers.	120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma concentrations of afamelanotide	To confirm the pharmacokinetics of afamelanotide by assessing afamelanotide plasma concentration following administration of the final formulation afamelanotide bioresorbable implants in healthy volunteers.	60 days
Number of Adverse Events	To confirm the tolerance of afamelanotide by assessing adverse events following administration of the final formulation afamelanotide implants in healthy volunteers.	60 days

Collaborators and Investigators

• Sponsor: Clinuvel Pharmaceuticals Limited
• Investigators: Principal Investigator: Mark A Matson, MD, Prism Research Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 29, 2010
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 16, 2018

Study Record Updates

• Last Update Posted (Actual): August 16, 2018
• Last Update Submitted That Met QC Criteria: August 14, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Afamelanotide; Nontherapeutic Human Experimentation in healthy volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Afamelanotide; alpha-MSH
• Other Study ID Numbers: CUV028