A Study to Learn How the Study Medicine Called PF-08653945 is Taken up Into the Blood in Adults With Overweight or Obesity

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2026-07-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety

To assess the relative bioavailability of a single PF-08653945 [CCI] mg dose administered SC to the thigh or upper arm compared to the abdomen.

Secondary objectives 1

1. To evaluate safety and tolerability of PF-08653945 administered SC to the abdomen, thigh, or upper arm.

Conditions and MedDRA coding

chronic weight management and other weight-related co-morbidities

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Participants 18 years of age or older at Screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECGs.
2. BMI of 27-45 kg/m2; and a total body weight >50 kg (110 lb). • For Japanese participants (Optional Cohort 2) only: BMI of 22-45 kg/m2 and a total body weight >50 kg (110 lb). NOTE: Participants enrolling as Japanese must have 4 biological Japanese grandparents who were born in Japan.

Exclusion criteria 18

1. Female who is lactating or who is pregnant (or planning to become pregnant during the trial) according to the pregnancy test at Screening or Day -1.
2. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal (pancreatitis and gallbladder disease), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). • History of HIV infection, hepatitis B, or hepatitis C; positive testing for HBsAg, HBcAb, HCVAb or HIV. Hepatitis B vaccination is allowed.
3. Personal or family history (first degree relatives) of MTC or MEN2, or participants with suspected MTC or the investigator’s judgement.
4. Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
5. Clinically significant gastric emptying abnormality (for example, gastric outlet obstruction).
6. Acute GI symptoms (eg, nausea, constipation, vomiting, diarrhea, heartburn) at the time of Screening, Day -1, or prior to administration of study intervention.
7. History of significant hypersensitivity reactions to drugs containing amylin agonists, calcitonin agonists or PF-08653945 excipients.
8. Use of any prescription or nonprescription drugs and dietary and herbal supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
9. Previous administration with a DACRA or amylin analogs within 90 days preceding the first dose of study intervention used in this study.
10. Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study intervention used in this study. Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.
11. Known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving PF-08653945.
12. A PHQ-8 score ≥15 obtained at Screening or Day -1.
13. Response of “yes” to question 4 or 5, or any suicidal behavioral question on the CSSRS over the last 12 months at Screening or Day -1. In addition, participants deemed by the investigator to be at significant risk of suicidal or violent behavior should be excluded.
14. A positive urine drug test at Screening or Day -1.
15. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants <60 years; and ≥150/90 mm/Hg for participants ≥60 years old, following at least 5 minutes of supine rest. If systolic BP is ≥ 140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant’s eligibility.
16. An eGFR (<60 mL/min/1.73 m²) as determined by the CKD-EPI equation using Screat.
17. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (including, but not limited to, QTcF >450 ms, complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST segment and/or T wave changes suggestive of myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant’s eligibility. Computer-interpreted ECGs with abnormal findings should be overread by an investigator experienced in reading ECGs before excluding a participant.
18. Participants with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: • ALT or AST ≥1.5 × ULN; • Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert’s syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ULN; • HbA1c ≥6.5%; • Fasting blood glucose ≥126 mg/dL (7 mmol/L); • TSH 1.5 × ULN prior to dosing.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AUCinf (if data permit, otherwise AUClast) and Cmax of PF-08653945.

Secondary endpoints 1

1. Assessment of TEAEs: • Clinical safety laboratory tests, vital signs, 12-lead ECGs, C-SSRS, and PHQ-8.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

2 submissions — initial application plus substantial / non-substantial modifications