Trial Outcomes & Findings for A Study of the Effect of Tirzepatide on How the Body Handles Birth Control Pills in Healthy Female Participants (NCT NCT04172987)

Last Updated: 2023-03-27

Results Overview

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Ethinylestradiol (EE)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

Period 1 and Period 2: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose

Results posted on

2023-03-27

Participant Flow

Participant milestones

Participant milestones
Measure	Overall Study Lead In Period and Period 1: Participants received a 28-day packet of a combination oral contraceptive (OC) containing 21 days of tablets that consist of active ingredients (0.035 mg ethinyl estradiol (EE) and 0.25 mg norgestimate (NGM)) self-administered orally once-daily (QD) on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day. Period 2: Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered subcutaneously (SC).
Lead In Period STARTED	40
Lead In Period Received at Least One Dose of OC	40
Lead In Period COMPLETED	38
Lead In Period NOT COMPLETED	2
Period 1 STARTED	38
Period 1 Received at Least One Dose of OC	38
Period 1 COMPLETED	37
Period 1 NOT COMPLETED	1
Period 2 STARTED	37
Period 2 Received at Least One Dose of OC	37
Period 2 Received at Least 1 Dose of Tirzepatide	28
Period 2 COMPLETED	28
Period 2 NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Overall Study Lead In Period and Period 1: Participants received a 28-day packet of a combination oral contraceptive (OC) containing 21 days of tablets that consist of active ingredients (0.035 mg ethinyl estradiol (EE) and 0.25 mg norgestimate (NGM)) self-administered orally once-daily (QD) on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day. Period 2: Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered subcutaneously (SC).
Lead In Period Adverse Event	1
Lead In Period Protocol Violation	1
Period 1 Physician Decision	1
Period 2 Adverse Event	5
Period 2 Dosing Termination by Sponsor	4

Baseline Characteristics

A Study of the Effect of Tirzepatide on How the Body Handles Birth Control Pills in Healthy Female Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=40 Participants Lead In Period and Period 1: Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day. Period 2: Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered SC.
Age, Continuous	33.6 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Period 1 and Period 2: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose

Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Ethinylestradiol (EE)

Outcome measures

Outcome measures
Measure	OC (0.035 mg EE and 0.25 mg NGM) n=35 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day.	OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide n=21 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered SC.
Period 1 and Period 2, Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Ethinylestradiol (EE)	966 picogram hour per milliliter (pg*h/mL) Geometric Coefficient of Variation 40	811 picogram hour per milliliter (pg*h/mL) Geometric Coefficient of Variation 41

PRIMARY outcome

Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose

Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.

PK: Cmax of EE

Outcome measures

Outcome measures
Measure	OC (0.035 mg EE and 0.25 mg NGM) n=35 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day.	OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide n=24 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered SC.
Period 1 and Period 2, PK: Maximum Concentration (Cmax) of EE	119 picogram per milliliter pg/mL Geometric Coefficient of Variation 33	49.6 picogram per milliliter pg/mL Geometric Coefficient of Variation 63

PRIMARY outcome

Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose

Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.

PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Norelgestromin (NGMN)

Outcome measures

Outcome measures
Measure	OC (0.035 mg EE and 0.25 mg NGM) n=35 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day.	OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide n=26 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered SC.
Period 1 and Period 2, PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Norelgestromin (NGMN)	19900 pg*h/mL Geometric Coefficient of Variation 27	14600 pg*h/mL Geometric Coefficient of Variation 67

PRIMARY outcome

Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose

Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.

PK: Cmax of Norelgestromin (NGMN)

Outcome measures

Outcome measures
Measure	OC (0.035 mg EE and 0.25 mg NGM) n=35 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day.	OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide n=26 Participants Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered SC.
Period 1 and Period 2, PK: Cmax of Norelgestromin (NGMN)	2070 pg/mL Geometric Coefficient of Variation 27	892 pg/mL Geometric Coefficient of Variation 74

Adverse Events

Lead-in: OC ( 0.035 mg EE and 0.25 mg NGM)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Period 1: OC ( 0.035 mg EE and 0.25 mg NGM)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Period 2: OC ( 0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Lead-in: OC ( 0.035 mg EE and 0.25 mg NGM) n=40 participants at risk Participants received a 28-day packet of a combination oral contraceptive (OC) containing 21 days of tablets that consist of active ingredients (0.035 mg ethinyl estradiol (EE) and 0.25 mg norgestimate (NGM)) self-administered orally once-daily (QD) on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day.	Period 1: OC ( 0.035 mg EE and 0.25 mg NGM) n=38 participants at risk Participants received a 28-day packet of a combination oral contraceptive (OC) containing 21 days of tablets that consist of active ingredients (0.035 mg ethinyl estradiol (EE) and 0.25 mg norgestimate (NGM)) self-administered orally once-daily (QD) on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day.	Period 2: OC ( 0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide n=28 participants at risk Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered SC.
Gastrointestinal disorders Abdominal discomfort	5.0% 2/40 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	2.6% 1/38 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	14.3% 4/28 • Number of events 4 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Gastrointestinal disorders Abdominal distension	5.0% 2/40 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	10.7% 3/28 • Number of events 3 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Gastrointestinal disorders Abdominal pain	2.5% 1/40 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	2.6% 1/38 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	14.3% 4/28 • Number of events 5 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Gastrointestinal disorders Nausea	10.0% 4/40 • Number of events 4 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	2.6% 1/38 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	39.3% 11/28 • Number of events 13 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Gastrointestinal disorders Vomiting	2.5% 1/40 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	17.9% 5/28 • Number of events 6 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
General disorders Chills	0.00% 0/40 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	10.7% 3/28 • Number of events 3 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
General disorders Pain	0.00% 0/40 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	10.7% 3/28 • Number of events 3 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Infections and infestations Corona virus infection	0.00% 0/40 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	7.1% 2/28 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Metabolism and nutrition disorders Decreased appetite	5.0% 2/40 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	2.6% 1/38 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	21.4% 6/28 • Number of events 6 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/40 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	7.1% 2/28 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Nervous system disorders Headache	2.5% 1/40 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	10.5% 4/38 • Number of events 5 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	17.9% 5/28 • Number of events 5 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Nervous system disorders Somnolence	0.00% 0/40 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	7.1% 2/28 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Reproductive system and breast disorders Dysmenorrhoea	2.5% 1/40 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	2.6% 1/38 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	7.1% 2/28 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Reproductive system and breast disorders Menorrhagia	5.0% 2/40 • Number of events 3 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	2.6% 1/38 • Number of events 1 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	7.1% 2/28 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.
Reproductive system and breast disorders Vaginal haemorrhage	5.0% 2/40 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	0.00% 0/38 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.	7.1% 2/28 • Number of events 2 • Lead-In Up To 15 Weeks All participants who received OC and tirzepatide.