Safety and Pharmacokinetics Study of CPL207280 Compound in Healthy Volunteers.

Healthy Volunteers Clinical Trial

Official title:

One Centre, Single Ascending Dose and Double Blind Multiple Ascending Dose, Safety and Pharmacokinetics Phase I Study of CPL207280 Compound in Healthy Volunteers.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04622111
• Other study ID #: 01GPR2019
• Status: Completed
• Phase: Phase 1
• Start date: May 27, 2020
• Est. completion date: May 5, 2021

Study information

• Verified date: May 2021
• Source: Celon Pharma SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The planned study is to determine the safety and pharmacokinetic properties of CPL207280 compound after single and multiple (two weeks) administration in healthy volunteers.

Description:

This is to be one-centre, single ascending dose and double-blind multiple ascending dose two part study of CPL207280 compound in healthy volunteers. PART A is a single dose, open-label part with CPL207280 compound administered with dose escalation between cohorts.Additionaly assessing the effect of food and effect of metformin on bioavailability of CPL207280 is to be done in additional cohort. PART B is a multiple, double-blind part with CPL207280 compound administered for 14 days with dose escalation between cohorts. Participants in this part are to be randomized to receive Investigational Medicinal Product (IMP) or placebo in 3:1 ratio. Safety and pharmacokinetic properties of CPL207280 compound is to be determined following different doses in single oral IMP administration in PART A and different doses of IMP administered orally for two weeks in PART B.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: May 5, 2021
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Caucasian female or male

• Body-mass index (BMI): = 18.5 kg/m² and < 29.9 kg/m²,

• Physical examination without any clinically relevant abnormality,

• Clinical laboratory results in hematology or renal/hepatic test and clinical laboratory results in other tests without any clinically relevant abnormalities as assessed by Investigator,

• Non-smoker and non-user of tobacco products for at least 3 months before screening,

• Subject able to provide written informed consent after receiving information about the trial,

• Informed Consent Form signed and dated prior to Screening evaluations,

• Ability and willingness to comply with the requirements of the study protocol,

• Volunteer (or his/her partner) of childbearing potential willingness to use acceptable forms of contraception.

Exclusion Criteria:

• Known allergy, hypersensitivity, intolerance or contraindication to other drugs similar in structure or class to CPL207280 compound, or to any excipients of the formulation,

• Any known significant current or past acute or chronic disease or condition of the:

circulatory, respiratory, hematopoietic, endocrine, nervous and musculoskeletal system, alimentary and urinary tracts, allergic disease, genetic or psychiatric disorder that could influence the present general health condition, at the Investigator's discretion,

• A long QT interval analysis syndrome (in the interview) or is under the treatment with antiarrhythmic drugs,

• Current disease of the alimentary tract, liver or kidneys that may influence absorption, distribution and/or elimination of the studied drug, as assessed by the Investigator and documented in the medical history,

• Medical condition that requires administration of other drugs or use of any drug within the 4 weeks preceding the first IMP administration and during the entire study. Drugs commonly used with fast metabolism may be administered and is up to Investigator discretion (i.e. pain killers),

• Participation in other clinical trials, where at least one dose of study drug was administered, within 90 days preceding the screening phase,

• Blood drawn within 30 days prior to inclusion in this study (more or equal to 300 mL),

• Positive results from pregnancy test in female volunteers,

• Lactation in female volunteers,

• Hypotension or hypertension in medical history,

• Narcotic and alcohol addiction or abuse,

• Positive results of HBsAg, anti-HCV or anti-HIV tests,

• Positive drug screen or alcohol breath tests,

• Subjects who adhere to a special diet (e.g. low calories, vegetarian,etc.).

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• CPL207280
IMP is a tablet with CPL207280 as an Active Pharmaceutical Ingredient (API).
• Placebo
matching placebo tablet
• Metformin hydrochloride 750 mg
IMP is a tablet with Metformin hydrochloride as an Active Pharmaceutical Ingredient (API).

Locations

Country	Name	City	State
Poland	BioResearch Group Sp. z o.o.	Kajetany	Nadarzyn

Sponsors (2)

Lead Sponsor	Collaborator
Celon Pharma SA	National Center for Research and Development, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of maximum tolerated dose (MTD) or administration of the maximum dose provided in the protocol after single and multiple oral administration of IMP.	MTD is defined as the highest dose for which no more than 1 of the 6 treated volunteers (less than 1/3) exhibits dose limiting toxicity (DLT).	up to 48 hours after single administration of IMP in PART A and up to 48 hours after the last IMP administration in PART B
Primary	Safety and tolerability of IMP after single and multiple oral administration	Participants during hospitalization are to be closely observed to assure maximal safety and to collect occurrence of all adverse event. To follow-up on all study participants telephone calls with a request for information regarding their health condition are to be made.	up to 14 days in PART A and up to 28 days in PART B of the study
Secondary	Cmax - maximum plasma concentration	The maximum concentration of the CPL207280 compound in plasma after IMP administration, obtained directly from the measured concentrations.	up to 48 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 in PART B and up to 48 hours after the last IMP administration on Day 14 in PART B
Secondary	AUC(0-48) - area under the plasma concentration - time curve from time 0 to 48h after IMP administration	The AUC(0-48) is a measure of total plasma exposure to the drug from time point zero to 48 hours after IMP administration	up to 48 hours after administration of IMP in PART A and after the IMP administration determined on Day 14 in PART B
Secondary	AUC(0-24) - area under the plasma concentration - time curve from time 0 to 24h after IMP administration	The AUC(0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after IMP	up to 24 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1 and 8 in PART B
Secondary	AUC(0-inf) - area under the plasma concentration - time curve from time 0 to infinity time	The AUC(0-inf) is a measure of total plasma exposure to the drug from time point zero extrapolated to infinity.	up to 48 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 in PART B and up to 48 hours after the last IMP administration on Day 14 in PART B
Secondary	Tmax - time to reach maximum concentration	The Tmax is time to reach the maximum plasma concentration (Cmax), obtained directly from the actual sampling times.	up to 48 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 in PART B and up to 48 hours after the last IMP administration on Day 14 in PART B
Secondary	Kel - terminal elimination rate constant	Kel is to be estimated via linear regression of time versus log of concentration.	up to 48 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 in PART B and up to 48 hours after the last IMP administration on Day 14 in PART B
Secondary	T1/2 - The plasma elimination half-life	T1/2 is to be calculated as 0.693/Kel.	up to 48 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 in PART B and up to 48 hours after the last IMP administration on Day 14 in PART B
Secondary	C (1,t) - CPL207280 concentration	The concentration of CPL207280 on day t before product administration.	Determined on Day 2, 3, 4, 5, 6, 7, 9, 10, 11, 12 and 13 in PART B
Secondary	C (Tmax, t) - CPL207280 concentration	The concentration on day t measured on time Tmax which was calculated in PART A of the study.	Determined on Day 2, 3, 4, 5, 6, 7, 9, 10, 11, 12 and 13 in PART B
Secondary	Glucose AUEC -area under the effect-time curve after IMP administration	The AUEC is a measure of total glucose concentration from time point zero to 6 hours after IMP	up to 6 hours after administration of IMP in PART A and up to 6 hours after the IMP administration determined on Day 1, 8,14 in PART B
Secondary	Insulin AUEC -area under the effect-time curve after IMP administration	The AUEC is a measure of total insulin concentration from time point zero to 6 hours after IMP	up to 6 hours after administration of IMP in PART A and up to 6 hours after the IMP administration determined on Day 1, 8,14 in PART B
Secondary	Proinsulin AUEC -area under the effect-time curve after IMP administration	The AUEC is a measure of total proinsulin concentration from time point zero to 6 hours after IMP	up to 6 hours after administration of IMP in PART A and up to 6 hours after the IMP administration determined on Day 1, 8,14 in PART B
Secondary	C-peptide AUEC -area under the effect-time curve after IMP administration	The AUEC is a measure of total c-peptide concentration from time point zero to 6 hours after IMP	up to 6 hours after administration of IMP in PART A and up to 6 hours after the IMP administration determined on Day 1, 8,14 in PART B
Secondary	Glucagon AUEC -area under the effect-time curve after IMP administration	The AUEC is a measure of total glucagon concentration from time point zero to 6 hours after IMP	up to 6 hours after administration of IMP in PART A and up to 6 hours after the IMP administration determined on Day 1, 8,14 in PART B
Secondary	AUC(0-tau, t)- area under the curve of plasma concentration vs time, from time point zero up to the time of 24h in day t	AUC(0-tau, t) will be calculated according to the linear trapezoidal rule	up to 24 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 and 14 in PART B
Secondary	Cav,t, averate IMP concentration on day t	Cav,t, will be calculated as AUC(0-tau, t)/24h.	up to 24 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 and 14 in PART B
Secondary	Fluctuation	Fluctuation will be calcilated as a difference between C(Tmax,t) and C(1,t) relative to the Cav,t, calculated as (C(Tmax,t)-C(1,t))/Cav,t x 100%.	up to 24 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 8 and 14 in PART B