A study to primarily determine how safe and tolerable the study treatment, PTG-200 is in comparison to a matching placebo, when taken by healthy participants as a single dose or multiple dose treatment.
A Phase 1 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PTG-200 in Normal Healthy Male Volunteers
Protagonist Therapeutics
80 participants
Nov 8, 2017
Interventional
Conditions
Summary
PTG-200 is an experimental drug being developed by Protagonist Therapeutics as a treatment for moderate to severely active Crohn’s Disease (CD) which is an inflammatory bowel disease (IBD). CD causes gastrointestinal signs and symptoms such as diarrhoea, abdominal pain, weight loss and passing blood or mucous. Current treatments for this highly complex disease have unacceptable side effects or cannot be used long term as they suppress the immune system and may increase the risk of serious infection or cancer. PTG-200 is believed to reduce the swelling that contributes to CD by blocking a specific part of your immune response pathway. There are a number of new treatments for CD which have been approved for use in other countries . PTG-200 is thought to be a better treatment for CD compared to these other medications as PTG-200 is restricted to the gut and very unlikely to spread to other parts of the body, meaning it would have fewer side effects and remain in the gut. The primary purpose of the study is to evaluate the safety and tolerability of the study drug referred to as PTG-200 in healthy individuals using single or multiple dose over number of days. The study will also evaluate how the PTG-200 is absorbed, spread in the body, and the body’s response to the drug.
Eligibility
Inclusion Criteria9
- Male normal healthy volunteers (NHV), age 18 to 55 years, inclusive.
- Participants must be in good general health, with no significant medical history, have no clinically significant abnormalities on physical examination at screening, and/or before administration of the initial dose of study drug.
- Participants must have a Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive.
- Participants must have clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator.
- Male participants with female partners should use a condom during sexual intercourse for 3 months after the last dose of study drug. In addition, male participants with female partners must agree to use a second highly-effective method of contraception (e.g. hormonal contraception or an intrauterine device) for 3 months after the last dose of study drug.
- Participants must be a non-smoker, and must not have regularly used nicotine products within six months prior to screening; those who have had social or accidental exposure to nicotine/nicotine-containing products over the 3 months prior to screening may be enrolled in the study at the discretion of the Investigator.
- Participants must have no dietary restrictions, and be willing to consume the standard meals provided.
- Participants must have the ability and willingness to attend the necessary visits to the study centre.
- Written informed consent signed prior to entry into the study.
Exclusion Criteria17
- History of clinically significant endocrine, neurological, gastrointestinal, cardiovascular, haematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases. Participants with a history of gastrointestinal disease including inflammatory bowel disease (IBD), toxic megacolon, dysplasia, gastroesophageal reflux disease (GERD), colon cancer, intestinal stenosis, or fistula will be excluded. History of surgical resection of the stomach, small or large intestine (excluding appendectomy, cholecystectomy, or resection of benign polyps) will be excluded. Note: NHVs with histories of uncomplicated kidney stones or childhood asthma may be enrolled in the study at the discretion of the Investigator.
- History of neoplastic disease, with the exception of adequately treated non melanomatous skin carcinoma.
- Mentally or legally incapacitated, has significant emotional problems at the time of Screening Visit or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder within the last 5 years. Note: NHVs who have had situational depression may be enrolled in the study at the discretion of the Investigator.
- Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening; evidence of intestinal infection within 30 days prior to screening.
- History of severe allergic or anaphylactic reactions
- Blood pressure (BP) >140/90 mm Hg or heart rate (HR) >100 beats per minute at Screening and at Day -1
- Clinically significant laboratory abnormalities including:
- a) Impaired renal function (serum creatinine levels >106 µmol/L) at Screening; estimated creatinine clearance (CrCl) of <80 mL/minute based on the Cockcroft-Gault equation below:
- Males: CrCl = (140 - age [years]) (body weight [kg])/(72)(serum creatinine [mg/dL])
- b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) laboratory values >1.2 × upper normal limits
- Clinically significant abnormality on ECG performed at the Screening Visit or prior to administration of the initial dose of study drug. (Screening and predose ECG conduction intervals must be within gender specific normal ranges [QT interval corrected for heart rate (QTc) in males less than or equal to 450 msec], however participants with out of normal range PR which is deemed not clinically significant by the PI may be enrolled).
- Positive test for hepatitis B surface antigen or human immunodeficiency virus (HIV) antibody at Screening. Patients positive for hepatitis C antibody are excluded unless they have had a history of sustained virologic response 12 weeks (SVR12) after the end of treatment for a prior infection.
- Participants with a positive toxicology screening panel (urine test including qualitative identification of barbiturates, tetrahydrocannabinol (THC), amphetamines, benzodiazepines, opiates and cocaine).
- Participants with a history of substance abuse or dependency or history of recreational intravenous drug use (by self-declaration).
- Regular alcohol consumption by males defined as >21 alcohol units per week (where 1 unit = 284 mL of beer, 25 ml of 40% spirit or a 125 ml glass of wine).
- Unable to refrain from or anticipates the use of any medications, including prescription and non-prescription drugs and herbal remedies (such as St. John’s Wort [Hypericum perforatum]), beginning 14 days (or 5 half-lives, whichever is longer) before administration of the initial dose of study drug and continuing throughout the study until the final study visit. There may be certain medications that are permitted at the discretion of the Investigator and Sponsor (including paracetamol/acetaminophen, medications for the treatment of AEs following administration of study drug, and multivitamins).
- Participants who are unlikely to comply with the study protocol or, in the opinion of the Investigator, would not be a suitable candidate for participation in the study.
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Interventions
Part 1: Single Ascending Dose Participants will be randomised to receive a single dose of PTG-200 or placebo capsule. Three cohorts of eligible participants are planned: Cohort 1: 150 mg PTG-200 or placebo Cohort 2: 300 mg PTG-200 or placebo Cohort 3: 900 mg PTG-200 or placebo. Participants, in Cohort 3 only, will return to the clinic after at least 7 days and will be administered a second single dose of 900 mg PTG-200 immediately following the consumption of a standard high fat meal. Part 2: Multiple Ascending Dose Participants will be randomised to receive oral administration of PTG-200 or placebo capsule daily for 14 days. Participants are not required to fast for dosing purposes. Four cohorts of eligible participants are planned: Cohort 4: 150 mg PTG-200 or placebo once daily Cohort 5a: 300 mg PTG-200 or placebo once daily Cohort 5b: 150 mg PTG-200 or placebo twice daily Cohort 6: 900 mg PTG-200 or placebo once daily; or 450 mg PTG-200 or placebo twice daily. Cohorts 5a and 5b will be conducted in parallel and the dose of Cohort 6 will be based on their results. Part 3: Formulation Cross-Over Part 3 will be a cross over of 2 formulations (tablet and capsule) consisting of the same active pharmaceutical ingredients (API). Part 3 will evaluate the bioavailability of the capsule formulation compared to the tablet formulation. Approximately 10 participants will be enrolled into a single dose cross-over cohort. Participants will be randomized to receive either PTG-200 300 mg capsule formulation or PTG-200 300 mg tablet formulation (5 participants to receive each). Participants will remain in the clinic until Day 3. A minimum of 7 days after the first dose, they will return for the second dosing period and receive a single dose of the alternate formulation of PTG-200, i.e., participants who received the capsule formulation for the first dose will then receive the tablet formulation, and vice versa. The duration of Part 3 is approximately 14 days. Part 3 is not double-blind and does not include placebo.
Locations(1)
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ACTRN12617001426370