Bioequivalence and Pharmacokinetic Study of Prurisol™ and Abacavir Sulfate in Healthy Volunteers

NCT02101216 | Completed Phase 1 DMC

• 1 other identifier: CTIX-14-03
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Cellceutix Corporation has created a new chemical entity for the treatment of psoriasis, termed Prurisol™, which is an ester of abacavir. This first-in-human study of Prurisol (abacavir acetate) is being performed to evaluate the pharmacokinetics, safety and tolerance of a single oral doses of Prurisol administered to healthy volunteers and the bioequivalence to abacavir sulfate (Ziagen). This study will be followed by a 505(b)(2) Phase 2 trial in patients with moderate to severe plaque psoriasis.

Conditions

Psoriasis

Keywords

bioequivalence; pharmacokinetics; psoriasis

Outcome Measures

Primary Outcomes (3)

• Area under the plasma concentration versus time curve (AUC) of abacavir derived from Prurisol and Ziagen

  Part B of the study will determine the average bioequivalence of abacavir derived from Prurisol (abacavir acetate) 350mg compared with abacavir derived from the commercially available tablet formulation of Ziagen (abacavir sulfate) 300mg. After completion of Part A, subjects will be randomly assigned to cross-over treatment sequence Prurisol then Ziagen, or Ziagen then Prurisol. Five to 21 days later, each subject will receive the alternate study drug. Evaluable subjects in the PK population will be those who received both alternate treatments and for whom an adequate number of post-dose PK sample results are available.

  24 hours after second and third dose of study drug or reference drug

• Peak plasma concentration (Cmax) of abacavir derived from Prurisol and Ziagen

  Part B of the study will determine the average bioequivalence of abacavir derived from Prurisol (abacavir acetate) 350mg compared with abacavir derived from the commercially available tablet formulation of Ziagen (abacavir sulfate) 300mg. After completion of Part A, subjects will be randomly assigned to cross-over treatment sequence Prurisol then Ziagen, or Ziagen then Prurisol. Five to 21 days later, each subject will receive the alternate study drug. Evaluable subjects in the PK population will be those who received both alternate treatments and for whom an adequate number of post-dose PK sample results are available.

  24 hours after second and third dose of study drug or reference drug

• Time to Cmax (Tmax) of abacavir derived from Prurisol and Ziagen

  Part B of the study will determine the average bioequivalence of abacavir derived from Prurisol (abacavir acetate) 350mg compared with abacavir derived from the commercially available tablet formulation of Ziagen (abacavir sulfate) 300mg. After completion of Part A, subjects will be randomly assigned to cross-over treatment sequence Prurisol then Ziagen, or Ziagen then Prurisol. Five to 21 days later, each subject will receive the alternate study drug. Evaluable subjects in the PK population will be those who received both alternate treatments and for whom an adequate number of post-dose PK sample results are available.

  24 hours after second and third dose of study drug or reference drug

Secondary Outcomes (7)

• Area under the plasma concentration versus time curve (AUC) of abacavir derived from Prurisol

  0 to 24 hours after the first dose of study drug

• Peak plasma concentration (Cmax) of abacavir derived from Prurisol

  0 to 24 hours after the first dose of study drug

• Time to Cmax (Tmax) of abacavir derived from Prurisol

  0 to 24 hours after the first dose of study drug

• Elimination half-life (t1/2) of abacavir derived from Prurisol

  0 to 24 hours after the first dose of study drug

• Number of participants with adverse events

  Day 1, Day 2, Day 3

Study Arms (5)

Pharmacokinetics of low dose Prurisol

EXPERIMENTAL

Pharmacokinetics of single dose of Prurisol™ 50 mg (1 tablets) to 6 subjects

Drug: Prurisol

Pharmacokinetics medium dose Prurisol

EXPERIMENTAL

Pharmacokinetics of single dose of Prurisol™ 100 mg (2 tablets) to 6 subjects

Drug: Prurisol

Pharmacokinetics of high dose Prurisol

EXPERIMENTAL

Pharmacokinetics of single dose of Prurisol™ 200 mg (4 tablets) to 6 subjects

Drug: Prurisol

Bioequivalence of Prurisol (350 mg)

EXPERIMENTAL

Single dose of Prurisol™ 350 mg (7 x 50 mg tablets)

Drug: Prurisol

Bioequivalence of Ziagen (300 mg)

ACTIVE COMPARATOR

Single dose of Ziagen 300 mg (1 x 300mg tablet)

Drug: Ziagen

Interventions

Prurisol DRUG

Experimental Drug

Also known as: abacavir acetate

Bioequivalence of Prurisol (350 mg); Pharmacokinetics medium dose Prurisol; Pharmacokinetics of high dose Prurisol; Pharmacokinetics of low dose Prurisol

Ziagen DRUG

Active comparator

Also known as: abacavir sulfate

Bioequivalence of Ziagen (300 mg)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals who meet ALL of the following criteria are eligible for participation in this study:
• Provided written informed consent
• Male or female adult aged 18-65 years old (inclusive). At least 20% of enrolled subjects will be aged 55-65 years, inclusive. Effort will be made to enroll equivalent numbers of males and females
• BMI of 19-32 kg/m2
• Identified as a non-smoker at the Consent/Screening Visit. A urine cotinine test will be performed at screening and during each clinic check-in before for each of the three Treatment Visits
• Willing and able to comply with all aspects of the study protocol including avoiding use of certain concomitant medications and attending the required clinic visits

You may not qualify if:

• Subjects are not eligible for participation in the study if any of the following criteria are met:
• Females of childbearing potential not using reliable contraception, (e.g., abstinence, double barrier method, oral/implantable/transdermal contraception. Depo-provera, intrauterine device)
• Female who is pregnant, lactating, has a positive serum pregnancy test drawn at the Consent/Screening Visit, or has a positive urine pregnancy test at check-in performed prior to any of the 3 Treatment Days
• Presence of any uncontrolled (in the Investigator's medical opinion) systemic disease, including, but not limited to renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or psychiatric disease
• History of any immune disorder, or disease/condition potentially affecting the immune system
• Regular use of oral or parenteral corticosteroids (inhaled corticosteroids for stable asthma or chronic obstructive pulmonary disease are permitted)
• ECG obtained at Consent/Screening Visit which shows medically significant abnormalities (e.g. bundle branch block, frequent premature ventricular contractions, corrected QT interval (QTc) prolongation \>450 msec for males and \>470 msec for females)
• Presence of a condition that makes it unlikely that the requirements of the protocol will be completed
• Urine screening test(s) positive for evidence of amphetamines, barbiturates, benzodiazepines, cocaine, methamphetamine, opiates, phencyclidine, marijuana
• Positive urine cotinine test
• Positive breath alcohol test
• History of hypersensitivity to any formulation of abacavir
• Previous treatment with any abacavir-containing product
• Current participation or participation in a drug/device or biologic investigational research study within 30 days prior to the Treatment A Visit
• An elective surgical or medical procedure is planned or scheduled to be performed during the period of the study

Sponsors & Collaborators

• Cellceutix Corporation: lead

Study Sites (1)

Phase One Solutions Inc.

Miami Gardens, Florida, 33169, United States

Location

Related Publications (6)

• Foster RH, Faulds D. Abacavir. Drugs. 1998 May;55(5):729-36; discussion 737-8. doi: 10.2165/00003495-199855050-00018.

  PMID: 9585869 BACKGROUND

• Galadari I, Rigel E, Lebwohl M. The cost of psoriasis treatment. J Eur Acad Dermatol Venereol. 2001 Jul;15(4):290-1. No abstract available.

  PMID: 11730031 BACKGROUND

• Hetherington S, McGuirk S, Powell G, Cutrell A, Naderer O, Spreen B, Lafon S, Pearce G, Steel H. Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir. Clin Ther. 2001 Oct;23(10):1603-14. doi: 10.1016/s0149-2918(01)80132-6.

  PMID: 11726000 BACKGROUND

• Imamichi T. Action of anti-HIV drugs and resistance: reverse transcriptase inhibitors and protease inhibitors. Curr Pharm Des. 2004;10(32):4039-53. doi: 10.2174/1381612043382440.

  PMID: 15579086 BACKGROUND

• Sonkoly E, Bata-Csorgo Z, Pivarcsi A, Polyanka H, Kenderessy-Szabo A, Molnar G, Szentpali K, Bari L, Megyeri K, Mandi Y, Dobozy A, Kemeny L, Szell M. Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS. J Biol Chem. 2005 Jun 24;280(25):24159-67. doi: 10.1074/jbc.M501704200. Epub 2005 Apr 26.

  PMID: 15855153 BACKGROUND

• Tzu J, Kerdel F. From conventional to cutting edge: the new era of biologics in treatment of psoriasis. Dermatol Ther. 2008 Mar-Apr;21(2):131-41. doi: 10.1111/j.1529-8019.2008.00180.x.

  PMID: 18394087 BACKGROUND

Related Links

• Ziagen® Highlights of Prescribing Information
• Ziagen® NDA # 020977 (December 1998),
• CDER FDA Guidance for Industry (January 2001). Statistical Approaches to Establishing Bioequivalence

MeSH Terms

Conditions

Psoriasis

Interventions

abacavir hydroxyacetate; abacavir

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Krishna Menon

  Cellceutix Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2014
• First Posted: April 2, 2014
• Study Start: March 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 26, 2018

Record last verified: 2018-10

Locations

US (1)