None listed
Conditions
Brief summary
This is a single-center, double-blind, randomised, matched vehicle-controlled study designed to assess the safety, tolerability, and pharmacokinetics of GDD3898 topical gel following twice daily application for 12 weeks in over-weight or obese subjects with presumed NAFLD. The study will enrol 24 adult male or female over-weight or obese subjects including those with presumed Nonalcoholic Fatty Liver Disease who are 18 to 70 years of age. Subjects will be enrolled in two cohorts and will be treated with 1.75% GDD3898 topical gel twice daily or identical vehicle gel twice daily. After completion of treatment, all subjects will have a follow up visit 14 days after last application of study drug.
Interventions
This is a single-center, double-blind, randomised, vehicle-controlled study designed to assess the safety, tolerability, and pharmacokinetics of GDD3898 topical gel following twice daily application for 12 weeks in over-weight or obese subjects with presumed Nonalcoholic Fatty Liver Disease.
The study will be comprised of two cohorts:
Cohort 1:
12 subjects will be randomised to receive either 1.75% GDD3898 topical gel or vehicle which will be applied to the subject's face, over an area of app
This is a single-center, double-blind, randomised, vehicle-controlled study designed to assess the safety, tolerability, and pharmacokinetics of GDD3898 topical gel following twice daily application for 12 weeks in over-weight or obese subjects with presumed Nonalcoholic Fatty Liver Disease. The study will be comprised of two cohorts: Cohort 1: 12 subjects will be randomised to receive either 1.75% GDD3898 topical gel or vehicle which will be applied to the subject's face, over an area of approximately 540cm2, approximately every 12 hours for 84 consecutive days. Cohort 2: 12 subjects will be randomised to receive 1.75% GDD3898 topical gel or vehicle which will be applied to the subject’s anterior aspect of one thigh, over an area of approximately 1260 cm2, approximately every 12 hours for 84 days. In both cohorts, subjects will be confined in the unit beginning on Day -1 and will be discharged on Day 8. Follow up visits will occur on Day 14, 28, 42, 56, 70, and 84. During the out-patient period, study medication tubes will be weighed at each clinic visit to monitor compliance. Additionally, subjects will complete a daily diary recording the date and time of each dose applied, any missed doses, and a comment section should the subjects have a comment, e.g., recorded potential Adverse Events (AE's). The study team will review the diaries and use the information to question the subject regarding compliance and AEs and then record appropriate information in the participants study notes. After completion of treatment, all subjects will have a follow up visit on Day 85, 86, and 98.
Sponsors
Lipidio Pharmaceuticals Australia Pty Ltd.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Man or woman 18 to 60 years of age at the time of consent. 2. Body mass index (BMI) >/= 27.0 and < /= 41.0 kg/m2 at screening. 3. Alanine aminotransferase (ALT) >/= 30 IU/mL. 4. MRI-PDFF value of 6% or higher. 5. Women of childbearing potential are required to use a protocol-approved highly effective contraceptive method for at least 4 weeks prior to screening until at least 4 weeks after the last application. 6. Males with female partners of childbearing potential must use reliable forms of contraception from screening to 4 weeks after the end of treatment. 7. Willingness to undergo skin biopsies of the thigh(s).
Exclusion criteria
1. Subject is a woman who is breastfeeding, pregnant, or who is planning to become pregnant during the study. 2. Subject has a history of skin disease or presence of skin condition (e.g., atopic dermatitis, psoriasis, etc.) that, in the opinion of the Investigator, would interfere with the study assessments. 3. Subject has had corneal or eyelid surgery, such as eyelid repair, reconstruction, and/or lifts, corneal transplantation, laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy, and/or radial keratotomy surgery, and/or has a history or presence of dry eye. 4. Subject has any history or evidence of hepatic cirrhosis and/or portal hypertension or complications (e.g. ascites, GI bleeds) or clinically meaningful hepatic impairment including: a. ALT and/or AST >3 x ULN b. Direct Bilirubin >/=6.9 mg/dL c. Albumin < 3.6 g/dL d. INR >/= 1.4 e. Platelets < 140 x109/mm3 f. FIB-4 >/= 2.67 g. If available, Histology: fibrosis score >/= 4 or Ishak score 5 or 6 h. Transient elastography >16 kPa Note: Subjects with documented Gilbert’s Syndrome (elevated unconjugated hyper-bilirubinemia but normal conjugated bilirubinemia) will be allowed to participate in the study. 5. History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV) infection, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), alcoholic liver disease, or definite autoimmune liver disease. 6. Subject with known history of or positive results for human immunodeficiency virus (HIV). 7. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening, other substance abuse within the prior two years of Screening, or positive urine drug, cotinine, or alcohol test at Screening. Significant alcohol consumption is defined as > 2 drinks/day or > 14 drinks/week for men and > 1 drink/day or > 7 drinks/week for women. 8. Prior or planned (during the study period) bariatric surgery (e.g., gastric bands, gastroplasty, roux-en-Y gastric bypass) or ileal resection. 9. Presence of scars, birthmarks, tattoos, or excessive hair at the application site(s) that would impede the assessment of local tolerability assessments. 10. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localised carcinoma in situ of the cervix may be included. 11. Subject had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study. 12. Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the Investigator, put the subject at undue risk by study participation or interfere with interpretation of study results (e.g., QTcF >450 msec for men or >470 msec for women). 13. Subjects with uncontrolled diabetes mellitus defined as hemoglobin A1c > 8.5%, hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg), or history of cardiovascular disease at Screening. 14. Subject has a known or suspected allergy to GDD3898 or any component of the study drug or the vehicle. 15. Unable to refrain from or anticipates the use of: a. Any drugs known to be moderate/strong inhibitors of CYP3A4 enzymes (such as boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) for 14 days or 5 times the half-life of the product (whichever is longer) prior to the first dose of study drug, throughout the period of dose application and until the last PK blood draw is collected. b. Any drugs known to be significant (i.e., strong or moderate) inducers of CYP enzymes, including St. John’s Wort, for 28 days prior to the first dose of study drug, throughout the period of dose application and until the last PK blood draw is collected. 16. Recent use of any medications that may promote fatty liver disease, such as systemically administered glucocorticoids, estrogens, etc. 17. Subjects who have major and/or clinically significant psychiatric disorders which would impede conduct of the research, including but not limited to, uncontrolled depression, suicidal ideation or uncontrolled bipolar disease at Screening. 18. Blood donation within 60 days prior to dosing or plasma donation within 14 days prior to dosing and during the study participation. 19. Subject has worn contact lens within 10 days prior to screening and/or is unable to avoid wearing them throughout the period of dose application and until the end of study ophthalmological examination. 20. Subject has any other known unstable medical condition that, in the opinion of the Investigator, puts the subject at undue risk or may limit the ability of the subject to comply with the protocol at Screening. 21. Following conditions or behavior likely to affect conduct of study: a. Weight loss or weight gain of > 10% in the past 6 months b. Unable to walk without assisted device c. Have plans to make a significant lifestyle change to their diet and exercise regimens during the study 22. Subject has pyrexia, cough, malaise or any other symptoms or signs consistent with SARS-CoV-2 viral infection at any time within 14 days prior to screening or baseline visits.
Outcome results
None listed