Phase 1 N=8 Basic Science

Study Evaluating the Pharmacokinetic and Mass Balance of Single Dose [14C] AZD9291 in Volunteers

Healthy Volunteers

Bottom Line

View on ClinicalTrials.gov: NCT02096679 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jul 2015

Primary outcome: Primary: Percentage of Radioactive Dose of [14C] Radiolabelled AZD9291 Recovered in Urine, Faeces, and in Total. — 14.2; 67.8; 81.9 Percentage radioactive dose recovered

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: AZD9291 (Drug)
Age: Adult, Older Adult · 30+ yrs
Sex: Male
Sponsor: AstraZeneca
Primary completion: Aug 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Radioactive Dose of [14C] Radiolabelled AZD9291 Recovered in Urine, Faeces, and in Total.	14.2; 67.8; 81.9	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration AUC(0-t)	1580; 125; 113; 178000; 158000	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve From Time Zero to the Time of 72 Hours AUC(0-72)	1010; 72.1; 50.9; 9670; 10700	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve From Time Zero to 24 Hours AUC(0-24)	444; 24.4; 15.7; 1980; 2300	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Maximum Plasma Concentration (Cmax)	29.9; 1.41; .957; 217; 260	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Time to Cmax (Tmax)	6; 6; 36; 144; 132.02	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Lag Time Before Observation of Quantifiable Analyte Concentrations (Tlag)	0; .51; .76; 0; .25	—
SECONDARY Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Oral Clearance (CL/F)	26.7; .213; .231	—
SECONDARY Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Volume of Distribution (Vz/F)	2260; 146; 191	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Half-life (t1/2,λz)	61.2; 55.2; 82; 474; 562	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Rate Constant (λz)	.0115; .0129; .00854; .00147; .00125	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of AUC Metabolite to Parent Ratio, AZ7550 or AZ5104 AUC/AZD9291 AUC Adjusted for Differences in Molecular Weight (M/PAUC)	.0909; .0848	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Cmax Metabolite to Parent Ratio, AZ7550 or AZ5104 (M/PCmax)	.0471; .0319	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Cmax Ratio of Plasma AZD9291, AZ7550 or AZ5104 (PL) to Plasma Radioactivity (Cmax(PL)/Cmax(PR))	.138; .00648; .0044	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Cmax Ratio of Whole Blood Radioactivity (WBR) to PR Cmax (WBR)/Cmax(PR)	1.2	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of AUC Ratio of Plasma AZD9291, AZD7550 or AZD5104 (PL) to Plasma Radioactivity (PR) AUC(PL)/AUC(PR)	.00826; .000751; .000698	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of AUC Ratio of WBR to PR (AUC(WBR)/AUC(PR))	.917	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve AUC	1590; 143; 132; 190000; 174000	—
SECONDARY Pharmacokinetics of AZD9291, Its Metabolites and Urine [14C] Total Radioactivity by Assessment of Urine Concentration or Concentration Equivalent x Urine Volume (Aeu)	329; 167; 184; 3870	—
SECONDARY Pharmacokinetics of AZD9291 and Urine [14C] Total Radioactivity by Assessment of Percentage (or Fraction) of Actually Administered Dose / Radioactivity (Feu)	.823; .416; .460; 9.67	—

Summary

Study to evaluate the pharmacokinetic and Mass Balance of single dose [14C] AZD9291 in healthy male volunteers

Eligibility Criteria

Inclusion Criteria

1, Volunteers must be willing to use reliable methods of contraception (condom and spermicide), even if their partners are postmenopausal, surgically sterile, or using an effective hormonal method of contraception or intrauterine coil. 2. In addition, volunteers must agree to continue to take similar contraceptive precautions until 6 months after the last administration of AZD9291 and avoid procreative sex as well as sperm donation for 6 months.

Exclusion Criteria: 1, Any clinically relevant abnormalities in physical examination, vital signs, hematology,clinical chemistry, urinalysis or ECG at baseline in the opinion of the investigator. 2. Radiation exposure from clinical studies, including that from the present study, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. -

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Data sourced from ClinicalTrials.gov (NCT02096679). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.